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Review

Atopic Dermatitis Immune Dysregulation as Dengue Predisposing Factor

       

Authors Astuti RDI, Alam A, Ghozali M , Setiabudiawan B 

Received 31 August 2024

Accepted for publication 15 November 2024

Published 27 November 2024 Volume 2024:17 Pages 9875—9887

DOI https://doi.org/10.2147/JIR.S493946

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Professor Ning Quan

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Ratna Dewi Indi Astuti,1,2,* Anggraini Alam,3,* Mohammad Ghozali,4,* Budi Setiabudiawan3,5

1Doctoral Study Program, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, 40161, Indonesia; 2Department of Microbiology-Parasitology, Faculty of Medicine, Universitas Islam Bandung, Bandung, West Java, 40116, Indonesia; 3Department of Child Health, Faculty of Medicine, Universitas Padjadjaran & Hasan Sadikin General Hospital, Bandung, West Java, 40161, Indonesia; 4Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, 40161, Indonesia; 5Faculty of Medicine, President University, Cikarang Bekasi, West Java, 17550, Indonesia

*These authors contributed equally to this work

Correspondence: Anggraini Alam, Department of Child Health, Faculty of Medicine, Universitas Padjadjaran, Jl.Prof. Eyckman 38, Bandung, West Java, 40161, Indonesia, Email [email protected]

Introduction: The immune response is important in dengue’s clinical manifestation, and the immune dysregulation in Atopic Dermatitis (AD) can permit immune evasion by viruses. There have been many studies describing the immune response in AD and the pathomechanism of dengue, but AD as a predisposing factor for dengue and its severity have not been much discussed. This review investigates how immune dysregulation in AD may be a predisposing factor for Dengue and its severe outcomes.
Methods: We conducted a comprehensive analysis of studies from the past decade, focusing on dendritic cells (DCs), macrophages, mast cells (MCs), Innate Lymphoid Cell 2 (ILC-2), Natural Killer (NK) cells, interferon (IFN), interleukin (IL) 4, IL-13, and T helper (Th) 2 in AD patients with healthy subject as a comparison, using databases PubMed, Science Direct, and Google Scholar.
Results: We got 44 articles that met inclusion criteria. From those articles, we resumed that moderate and severe AD patients’ immune profiles showed increased DC, MCs, M2 macrophage, NK cells, and ILC2 in the lesional and non-lesional skin, decreased DC and NK cells in peripheral blood, alteration cytotoxicity of NK cells, Th2-skewed adaptive immune response in lesional and non-lesional skin, and peripheral blood. Increased DC, M2 macrophage, and MCs provide target cells for Dengue virus (DENV) replication. Alteration cytotoxicity of NK cells, ILC2, and Th2 skewed immune response facilitated immune evasion by DENV.
Conclusion: The innate and adaptive immune dysregulation in moderate and severe AD provides DENV target cells and facilitates virus immune evasion that can be a predisposing factor for dengue and severe dengue. Further research is recommended to clarify the association between AD and the incidence of dengue and severe dengue because this can be a consideration in determining the prognosis and management of Dengue.

Keywords: atopic dermatitis, adaptive immune response, dengue, innate immune response

Graphical Abstract:

Introduction

Dengue is a disease caused by the dengue virus, transmitted by the Aedes aegypti and Aedes albopictus mosquito, and has four serotypes namely DENV1 – DENV4.1,2 Dengue is a world health problem since it is endemic in over 100 countries. The incidence rate and geographical spreading of dengue have increased in the last decades. According to WHO estimation, as many as 50 million people are infected with DENV and 25,000 people die because of dengue.2,3 The clinical manifestations range of dengue is wide in humans, ranging from asymptomatic, fever, to plasma leakage and bleeding or severe dengue which can cause death.4–6

DENV infections are responded by the innate immune response and the Th1 adaptive immune response.7,8 However, the type 2 immune response facilitated the DENV to continue replicating. Because of this, the type 2 immune response is one of the pathomechanisms of dengue.9 Severe dengue is associated with innate immune response dysfunction,10 excessive NK cell activity,11 delayed Th1 response related to Th2 immune response,10,12,13 and high levels of viremia.11,14 Therefore, diseases with dysregulation of the immune response such as atopy, kidney disease, diabetes mellitus, and obesity become risk factors for severe dengue.15,16 Mosquito salivary proteins are also considered to have a part in dengue pathogenesis because they increase tissue cellularity at the site of the mosquito’s bite which provides target cells for DENV replication and Th2 skewed immune response.17–19

In AD, which is one of atopic diseases, immune dysregulation is found to increase the risk of infection.20 Type 2-skewed immune response is the hallmark of AD.21 Allergic skin disease, which has the same basic disease mechanism as AD, is correlated with the severity of dengue. Pruritus, which is one of the symptoms of AD, is also associated with dengue.22

The immune dysregulation in AD potentially facilitates immune evasion by viruses that could increase dengue’s incidence and severity. Studies regarding AD as a predisposing factor for dengue and its severity have not been widely described, however, there have been many studies explaining about immune profiles in AD and the pathomechanism of dengue. This article will discuss how the immune profile in AD could be a dengue predisposing factor and its severity. The understanding of the immune profile in AD, which is related to the immune response in dengue, can be used for further study to clarify the correlation between AD and dengue which is important in determining prognosis and management of dengue.

Materials and Methods

We reviewed the full text of the letters to the editor and original articles written in English about DC, macrophage, MC, ILC-2, NK cell, IFN, IL-4, IL-13, and Th2 profile of AD patients that could be an underlying factor for increasing dengue incidence and its severity, which are published within the last 10 years (January 1st 2014–July 31st 2024), with AD patients as the subject and healthy people as a comparison. We searched the literatures using PubMed database with keyword ((((atopic dermatitis[MeSH Terms]) OR (atopic eczema[MeSH Terms])) OR (atopic dermatitis[Title/Abstract])) OR (atopic eczema[Title/Abstract])) AND (((((((((((((((((((((((((((((((((immune response, innate[MeSH Terms]) OR (adaptive immune response[MeSH Terms])) OR (cell, dendritic[MeSH Terms])) OR (cell, dermal dendritic[MeSH Terms])) OR (cell, epidermal dendritic[MeSH Terms])) OR (mast cells[MeSH Terms])) OR (cell, natural killer[MeSH Terms])) OR (alpha interferon[MeSH Terms])) OR (interferon gamma[MeSH Terms])) OR (interleukin 4[MeSH Terms])) OR (interleukin 13[MeSH Terms])) OR (balance, th1 th2[MeSH Terms])) OR (cell, th1[MeSH Terms])) OR (cell, th2[MeSH Terms])) OR (innate immune response[Title/Abstract])) OR (adaptive immune response[Title/Abstract])) OR (dendritic cell[Title/Abstract])) OR (DC[Title/Abstract])) OR (DC-SIGN[Title/Abstract]))) OR (macrophage[Title/Abstract])) OR (mast cell[Title/Abstract])) OR (MC[Title/Abstract])) OR (innate lymphoid cell[Title/Abstract])) OR (ILC[Title/Abstract])) OR (natural killer cell[Title/Abstract])) OR (NK cell[Title/Abstract])) OR (interferon[Title/Abstract])) OR (IFN[Title/Abstract])) OR (interleukin 4[Title/Abstract])) OR (interleukin 13[Title/Abstract])) OR (th1[Title/Abstract])) OR (th2[Title/Abstract])) AND ((fft[Filter]) AND (humans[Filter]) AND (2014/1/1:2024/7/31[pdat]) AND (English[Filter])). We also searched literature from Google Scholar, citation searching, and the Science Direct database with keywords atopic dermatitis AND (dendritic cell OR macrophages OR mast cell OR natural killer cell OR innate lymphoid cell OR interferon OR interleukin OR T-helper) in addition to PubMed database.

Results

We reviewed 44 articles that describe immune profiles of AD patients that could be predisposing factors for dengue. The flow of our literature research is described in PRISMA flowchart (Figure 1). We resumed from those articles showing that there were innate immune dysregulations in lesional and non-lesional skin, and also in peripheral blood AD patients, especially in moderate and severe AD patients. There were M2-macrophages and DCs infiltration with increased DC-SIGN expression and an increased MCs number in lesional and non-lesional AD skin patients.23–30 In contrast, the number of DCs in peripheral blood severe AD patients decreased31 (Tables 1 and 2).

Table 1 Summary of DCs and M2-Macrophages Profile in AD

Table 2 Summary of MCs Profile in AD

Figure 1 PRISMA flowchart.

The ILC2 as one of some innate immune systems were increased in AD skin lesions.32,33 In peripheral blood AD patients, their number decreased but was still higher in ILC proportion.31,34 There were also decreased levels and alterations in type-1 interferon which is produced by innate immune cells35,36 (Table 3). Other innate immune dysregulations were in the number and function of NK cells. There was an increase in NK cell numbers in skin AD patients. In contrast, there was a decrease in NK cell number expression in peripheral blood with a high expression of skin-targeted NK cells. There was also a reduction of NK cytotoxic functions and an enhancement of resting-NK cell subpopulation37–44 (Table 4).

Table 3 Summary of ILCs and Type-1 Interferon Profile in AD

Table 4 Summary of NK Cells Profile in AD

There were also dysregulations in adaptive immune response in AD. There were gene up regulations and increased levels of IL4 and IL13 cytokines as the main cytokines in AD pathogenesis45–53 (Table 5). Other cytokines and chemokines increased that reflect the Th2 skewed adaptive immune response also occurred in AD patients54–67 (Table 6).

Table 5 Summary of IL4 and IL13 Levels as Main Cytokines of Th2-Adaptive Immune Response in AD

Table 6 Summary of Other Th2-Skewed Adaptive Immune Response in AD

Discussion

Innate Immune Dysregulation

Dendritic Cells and Macrophage M2 Infiltration in the AD Skin

The DENV enters the human body through the skin by mosquito bites. DCs, Langerhans Cells (LC), and macrophages, which are innate immune cells, are some of the target cells for Dengue virus in the skin. Dengue virus replicates in those cells and continues its life cycle.68–70 The virus will attach its glycoprotein E to specific receptors on LC, macrophages, and DCs in the dermis and epidermis which initiate endocytosis.7,71 The DENV receptors on target cells are Dendritic Cell-Specific Intercellular adhesion molecule-3 Grabbing Non-integrin (DC-SIGN), mannose receptor (MR), and C-type lectin domain family 5 member A (CLEC5A).69,70,72

After the DENV enters DCs, macrophages, and LCs, the viral antigen is recognized by pathogen-recognized receptors on the host cell and initiates the formation of type 1 IFN. Type 1 IFN initiates a signal to induce Interferon-stimulated genes (ISGs) which will create an antiviral state in the cell and surrounding cells, both infected and uninfected. ISG genes influence RNA production, protein turnover, and apoptosis, disrupting the life cycle and viral replication.7,71 Type 1 IFN also induces Th1 activation which will strengthen the fight against the virus.73 The infected cell host is also destroyed by NK cells to eliminate the virus.74 But viruses do some immune evasion, and there is some immune dysregulation that permits virus to stay alive and do replication.10,75

On the lesional and non-lesional skin of AD patients, DC proliferation was found,24,25,27 and expression of DC-SIGN increased.23 Activated M2 macrophage was also increased in lesional and non-lesional skin from AD patients.28 The increased levels of the cytokines IL4 and IL13 that occur in AD activate DC-SIGN and MR on DCs and macrophages.76 The increased IL4 levels can cause macrophages and DCs to become permissive to dengue infection.77

Skin barrier disorder, which happens in AD, contributes to the type 2 immune response polarization. The skin barrier disorder in AD is due to a congenital deficiency of filaggrin protein78,79 and environmental exposure.80 Skin barrier disorder causes allergens and pathogens to enter the skin and stimulates DCs to produce thymic stromal lymphopoietin (TSLP), IL33, and IL25.81 TSLP activates DCs and increases the number of DCs in the skin. Allergens that enter the skin due to barrier epithelial disruption also stimulate DCs activation. Those DCs direct differentiation of Th cell to Th2 cell by producing IL4 in lymph nodes. The activated Th2 cells produce more type 2 cytokines, IL4, IL5, and IL13.82

Even though there was an increased expression of DC-SIGN in the skin and decreased DC count in peripheral blood in AD patients,23,31 AD has not been said to increase or decrease the incidence of dengue.83 In contrast to AD, the decrease in the expression of DC-SIGN in peripheral blood DC in asthma and AR can reduce the risk of dengue infection. In a cohort study, it was found that the Hazard Ratio for asthma patients to get Dengue was 0.166 when compared to non-asthma.84 In a cross-sectional study, the Odds Ratio for getting dengue in asthma and AR patients was 0.45 and 0.48. Internalization of DC-SIGN, which binds to House Dust Mites as the main allergen of asthma patients, causes a decrease in the number of DC-SIGN on the surface of DCs in asthma patients.84,85

Infiltration of Mast Cells

MCs are also related to dengue.86 MCs are also some of the first innate immune cells that recognize the entry of the DENV into the skin. MCs can be infected by the DENV,87 but virus replication does not occur in MCs.88 The Dengue virus is found in the granules that are secreted by infected dengue MCs. These granules can enter the lymph vessels, suggesting that MCs may play a role in the systemic spread of the Dengue virus.87

MCs respond to the entry of the Dengue virus into the skin by secreting type I cytokines,88 and chemokines CCL3, CCL4, and CCL5 which attract monocytes, T cells, and NK blood cells. MCs also secrete histamine and Vascular Growth Endothelial Factor (VEGF), which increase vascular permeability allowing for the entry of monocytes, T cells, and NK cells into the skin from blood vessels to help kill viruses.77 In severe dengue, when the viral load increases due to failure of the immune response,10 the number of MCs increases, along with elevated level of chimase which is only secreted by MCs.10,86 Additionally, levels of VGEF and histamine rise, leading to increased blood vessel permeability.86

The increase in active MCs was found in AD lesional and non-lesional skin lesions,29,30 which play two important pathogenesis roles: protective effect and promoting inflammation.89 MCs maintain epithelial integrity and control Th2 inflammation.90 The MCs are activated by allergen binding to the IgE in Fcε RI on MCs.91 This binding stimulates MCs to produce IL4 and IL13 which direct Th2 activation. MCs also secrete histamine which causes vasodilation and increases blood vessel permeability as well as stimulate nerve endings which cause erythema, edema, and itching.89

The increase of MCs in AD may build protection against DENV infection.88,92 However, DENV can infect MCs,87 and there are other innate immune system defects in AD,20,35,36,93 which results in ineffective elimination of the Dengue virus. A high viral load and an increase in the number of MCs potentially develop severe dengue in AD. In addition to MCs as the target cell of Dengue virus, mast cell degranulation in response to mosquito saliva can cause wheal. Wheals caused by the response to mosquito’s saliva bring about flavivirus retention in the skin and increases replication.94 The wheal diameter is also in line with the number of DCs and M2-macrophages at the bite site that could be dengue target cells.17 M2-macrophages are not macrophages that have antiviral capabilities. M2-macrophages are different from classic macrophages (M1-macrophages) which have antiviral activity. M1-macrophages are activated by bacterial cell walls, lipoproteins, and IFN which phagocytose and produce Nitric Oxide to eliminate pathogens. M2-macrophages express arginase-1 and cytokine for tissue repair and are permissive to viruses.68,95

AD patients’ skin is not healthy, both lesional and non-lesional. The non-lesional skin also showed prolonged itch responses and increased receptors for proteases and histamine expression on cowhide provocation.30 Many people with AD also react to mosquito saliva as a type of allergen.96 Allergic reactions to mosquito saliva positively correlate with the severity of AD,97 leading to larger inflammatory wheals at mosquito bite sites and promoting DENV replication.17,98

Increment ILC-2

Other innate immune cells that are no less important are ILC1 which produces IFN-γ that induces ISG together with type I IFN to form an antiviral environment to eliminate viruses and direct the activation of Th1 adaptive immune cells. Activation of ILC2 helps Dengue virus to replicate, reach the bloodstream, and enhances viral infection in monocytes.9

In AD skin lesions, there is an increased number of ILC2.32,33, which is also observed increased proportion of ILC2 in the peripheral blood of severe AD patients.31 The increase in the number of ILC2s in AD is induced by Thymic stromal lymphopoietin production due to exposure to allergens or scratches on the lesion.99 In addition, ILC2 is an innate immune cell that produces type 2 cytokines (namely IL4, IL5, and IL13) and directs the activation of Th2 cells which are not effective in virus elimination.78 An increase in the number of ILC2s in AD can enhance the risk of dengue.

In contrast to the increase in type 2 cytokine in AD, the levels of type I IFN and IFN-γ were falling.35 DC in AD also demonstrated a decrease in type I IFN production.20,100 Although type I IFN gene expression increased in the lesional skin of AD, there are editing changes in the IFN RNA resulting in impairment of the innate immune system.36 A decrease in type I IFN levels in AD potentially increases the risk of dengue and severe dengue.

NK Cells Alteration

The number of NK cells in lesional and non-lesional skin AD patients increased,37,38,41,42 but NK-cell natural cytotoxicity and population were affected in severe AD.43,44,101 Peripheral blood NK cells are deficient,37,40,42 caused by migration to the skin43 and increased NK cell death.37 NK cells are cytotoxic ILCs that produce IFN-γ and other antiviral agents.74 NK cells can even inhibit viral replication enhancement due to the Antibody-dependent enhancement (ADE) mechanism.102 The decrease in the number of NK cells,103,104 and impaired NK cell response in early infection of Dengue virus can increase the risk of severe dengue.105,106

Th2-Skewed Adaptive Immune Response

Viral-infected DCs and LC in the skin will go to the lymph nodes in the directions of CCR7 and CCL21 chemokines and initiate an adaptive immune response. DCs present viral antigens to CD4 cells via major histocompatibility complex (MHC) class I and II in lymph nodes. CD4 cells that bind to MHC class II of viral-infected DCs will be activated into Th1 cells according to the induction of type 1 IFN cytokines which are released by DCs. Th1 cells produce IFN-γ and TNF which activate macrophage phagosomes and strengthen cytotoxic CD8 cells. Th1 cells will also move to the medulla and induce B cells to produce anti-dengue IgM and IgG to neutralize viruses and strengthen complement and CD8 cells to destroy viruses.8 CD8 cells that are formed and activated in the lymph nodes can also return to the skin at the initial infection site to clear the virus with the expression of CXCR3, CCR5, and the skin-homing marker cutaneous lymphocyte-associated antigen (CLA).68

If the immune response cannot control the virus, the virus will continue to replicate in the lymph nodes. As virus replication continues in the lymph nodes, the number of viruses increases and enters the blood circulation (viremia). In blood circulation, the virus infects blood vessel endothelial cells, monocytes, as well as macrophages, and DCs in other lymphoid organs such as the liver.8,107 The virus can escape the immune system by inhibiting the induction of ISGs, so the virus can continue to replicate by infecting macrophages and DCs in the skin and lymph nodes.75 Virus replication can even increase in secondary infections through the ADE mechanism.8,71

The viremia causes cell lysis and the production of inflammatory cytokines through complement activation and other immune responses which causes fever,12 vascular permeability that can lead to shock,11,108 and severe thrombocytopenia that can cause bleeding.13,14 Bleeding in dengue infection is also caused by a decrease in coagulation factors due to liver damage.14,73 Dengue, which is accompanied by bleeding and plasma leaking, is called severe dengue.8

The activation of the Th1 immune response can be inhibited by the IL4 as Th2 cytokine by increasing the GATA3 transcription factor which will suppress IFN-γ production and TBx21(T-bet) gene expression. On the other hand, IL12 as the Th1 cytokine can also reduce the Th2 immune responses by increasing the transcription factors T-bet and IFN-γ which reduce GATA3 expression and result in a decrease in IL4 cytokine production which inhibits Th2 cell activation.109

Polarization of the Th2 immune response is a hallmark in atopy patients. Allergens that enter the skin activate DCs and ILCs2 and direct the differentiation of Th cells into Th2 cells which produce IL4, IL5, IL13, and IL33 cytokines.110–113 The increased expression of Th2 genes or Th2 cytokines level not only occurs in AD skin lesions25,26,48,51–53,56,59,62,63 but also in non-lesional skin,26,52,56,67 and peripheral blood AD patients,33,39,45,47,49,52,54,55,57,58 especially moderate and severe AD patients.27,50,56–58,60,63,65–67 Th1 adaptive immune response inhibition by Th2 polarization occurs in AD. There was a decrease in IFN-γ.35 However, the disruption of the Th1 immune profile was variated. In pediatric AD patients, there was a decrease in Th1 expression.60,67 In contrast, Th1 levels were found to increase in adult AD patients,57,58,60,63,64 but the Th1/Th2 ratio remains decreased.65

The Th2 immune response to DENV is related to the dengue.12,114 Severe dengue correlates with the impairment of the Th1 immune response which is related to a Th2 polarization immune response. The severity of dengue infection is associated with a decrease in T-bet levels. T-bet is a transcription factor for the formation of the cytokine IFN-γ.115 The Th1 adaptive immune response impairment can be followed by an uncontrolled innate immune response by ILC and excessive NK cell activity.103 Excessive NK cell activity is also associated with severe dengue.11 The Th2 immune response polarization in AD may play a role in dengue and severe dengue pathogenesis.

Conclusion

Moderate-severe AD patients showed increased DCs, M2-macrophage, and MCs in the skin as they ported the entry of DENV. It may provide target cells for Dengue virus replication. Alteration in ILC2 and NK cells number and function, and also Th2 skewed immune response, which also occurs in moderate-severe AD patients facilitated immune evasion by Dengue virus. The innate and adaptive immune dysregulation in moderate and severe AD provides DENV target cells and facilitates virus immune evasion, which can be a predisposing factor for dengue and severe dengue. Further research needs to be carried out to clarify the correlation between AD and the incidence of dengue and severe dengue. AD on dengue needs to be considered in determining the prognosis and management of dengue infection.

Acknowledgments

This study was supported by funding from Universitas Padjadjaran Bandung, Jawa Barat, Indonesia.

Disclosure

The authors declare that they have no financial interest or other conflicts of interest for this work.

References

1. Murugesan A, Manoharan M. Dengue virus. In: Ennaji MM editor. Emerging and Reemerging Viral Pathogens. Academic Press; 2020:281–359. doi:10.1016/B978-0-12-819400-3.00016-8

2. Roy SK, Bhattacharjee S. Dengue virus: epidemiology, biology, and disease aetiology. Can J Microbiol. 2021;67(10):687–702. doi:10.1139/cjm-2020-0572

3. Jing Q, Wang M. Dengue epidemiology. J Glob Health. 2019;3(2):37–45. doi:10.1016/j.glohj.2019.06.002

4. Verhagen LM, De Groot R. Dengue in children. J Infect. 2014; 69:S77–S86. doi:10.1016/j.jinf.2014.07.020

5. Muller DA, Depelsenaire ACI, Young PR. Clinical and laboratory diagnosis of dengue virus infection. J Infect Dis. 2017;215(Suppl 2):89–95. doi:10.1093/infdis/jiw649

6. Guzman MG, Gubler DJ, Izquierdo A, Martinez E, Halstead SB. Dengue infection. Nat Rev Dis Primers. 2016;2:16055. doi:10.1038/nrdp.2016.55

7. Uno N, Ross TM. Dengue virus and the host innate immune response. Emerg Microbes Infect. 2018;7(1):1–11. doi:10.1038/s41426-018-0168-0

8. St. John AL, Rathore APS. Adaptive immune responses to primary and secondary dengue virus infections. Nat Rev Immunol. 2019;19:218–230. doi:10.1038/s41577-019-0123-x

9. Fonseka CL, Hardman CS, Woo J, et al. Dengue virus co-opts innate type 2 pathways to escape early control of viral replication. Commun Biol. 2022;5:735. doi:10.1038/s42003-022-03682-5

10. Malavige GN, Jeewandara C, Ogg GS. Dysfunctional innate immune responses and severe dengue. Front Cell Infect Microbiol. 2020;10:590004. doi:10.3389/fcimb.2020.590004

11. Srikiatkhachorn A, Thew A, Rothman AL. Immune mediated cytokine storm and its role in severe dengue. Semin Immunopathol. 2017;39(5):563–574. doi:10.1007/s00281-017-0625-1

12. Bhatt P, Sabeena SP, Varma M, Arunkumar G. Current understanding of the pathogenesis of dengue virus infection. Curr Microbiol. 2021;78:17–32. doi:10.1007/s00284-020-02284-w

13. Wang WH, Urbina AN, Chang MR, et al. Dengue hemorrhagic fever – a systemic literature review of current perspectives on pathogenesis, prevention and control. J Microbiol Immunol Infect. 2020;53(6):963–978. doi:10.1016/j.jmii.2020.03.007

14. Pathak B, Chakravarty A, Krishnan A. High viral load positively correlates with thrombocytopenia and elevated haematocrit in dengue infected paediatric patients. J Infect Public Health. 2021;14(11):1701–1707. doi:10.1016/j.jiph.2021.10.002

15. Zulkipli MS, Dahlui M, Jamil N, et al. The association between obesity and dengue severity among pediatric patients: a systematic review and meta-analysis. PLoS Negl Trop Dis. 2018;12(2):e0006263. doi:10.1371/journal.pntd.0006263

16. Yuan K, Chen Y, Zhong M, Lin Y, Id LL. Risk and predictive factors for severe dengue infection: a systematic review and meta- analysis. PLoS One. 2022;17(4):e0267186. doi:10.1371/journal.pone.0267186

17. Guerrero D, Vo HTM, Lon C, et al. Evaluation of cutaneous immune response in a controlled human in vivo model of mosquito bites. Nat Commun. 2022;13:7036. doi:10.1038/s41467-022-34534-9

18. Henrique MO, Neto LS, Assis JB, et al. Evaluation of inflammatory skin infiltrate following Aedes aegypti bites in sensitized and non-sensitized mice reveals saliva-dependent and immune-dependent phenotypes. Immunology. 2019;158:47–59. doi:10.1111/imm.13096

19. Demarta-Gatsi C, Mécheri S. Vector saliva controlled inflammatory response of the host may represent the Achilles heel during pathogen transmission. J Venom Anim Toxins Incl Trop Dis. 2021;27:1–17. doi:10.1590/1678-9199-JVATITD-2020-0155

20. Wang V, Boguniewicz J, Boguniewicz M, Ong PY. The infectious complications of atopic dermatitis. Ann Allergy Asthma Immunol. 2021;126:3–12. doi:10.1016/j.anai.2020.08.002

21. Kader HA, Azeem M, Jwayed SA, et al. Current insights into immunology and novel therapeutics of atopic dermatitis. Cells. 2021;10:1397. doi:10.3390/cells10061392

22. Kien ND, El-Qushayri AE, Ahmed AM, et al. Association of allergic symptoms with dengue infection and severity: a systematic review and meta-analysis. Virol Sin. 2020;35:83–92. doi:10.1007/s12250-019-00165-6

23. Zhang Y, Luo Y, Li W, et al. DC-SIGN promotes allergen uptake and activation of dendritic cells in patients with atopic dermatitis. J Dermatol Sci. 2016;84(2):128–136. doi:10.1016/j.jdermsci.2016.08.008

24. Guttman-Yassky E, Diaz A, Pavel AB, et al. Use of tape strips to detect immune and barrier abnormalities in the skin of children with early-onset atopic dermatitis. JAMA Dermatol. 2019;155(12):1358. doi:10.1001/jamadermatol.2019.2983

25. He H, Suryawanshi H, Morozov P, et al. Single-cell transcriptome analysis of human skin identifies novel fibroblast subpopulation and enrichment of immune subsets in atopic dermatitis. J Allergy Clin Immunol. 2020;145(6):1615–1628. doi:10.1016/j.jaci.2020.01.042

26. He H, Bissonnette R, Wu J, et al. Tape strips detect distinct immune and barrier profiles in atopic dermatitis and psoriasis. J Allergy Clin Immunol. 2021;147(1):199–212. doi:10.1016/j.jaci.2020.05.048

27. He H, Del Duca E, Diaz A, et al. Mild atopic dermatitis lacks systemic inflammation and shows reduced nonlesional skin abnormalities. J Allergy Clin Immunol. 2021;147(4):1369–1380. doi:10.1016/j.jaci.2020.08.041

28. Mitamura YMR, Kim J, Xiao Y, et al. Spatial transcriptomics combined with single- cell RNA- sequencing unravels the complex inflammatory cell network in atopic dermatitis. Allergy. 2023;78:2215–2231. doi:10.1111/all.15781

29. Luo X, Chen J, Yang H, et al. Dendritic cell immunoreceptor drives atopic dermatitis by modulating oxidized CaMKII-involved mast cell activation. JCI Insight. 2022;7(5):e152559. doi:10.1172/jci.insight.152559

30. Moon S, Stasikowska-Kanicka O, Wągrowska-Danilewicz M, et al. Clinically uninvolved but not healthy—The skin of patients with atopic dermatitis is primed for itch and inflammation. J Eur Acad Dermatol Venereol. 2024;38(6):1089–1100. doi:10.1111/jdv.19694

31. Jin SP, Lee K, Bang YJ, et al. Mapping the immune cell landscape of severe atopic dermatitis by single‐cell RNA‐seq. Allergy. 2024;79:1584–1597. doi:10.1111/all.16121

32. Brüggen MC, Bauer WM, Reininger B, et al. In situ mapping of innate lymphoid cells in human skin: evidence for remarkable differences between normal and inflamed skin. J Invest Dermatol. 2016;136:2396–2405. doi:10.1016/j.jid.2016.07.017

33. Alkon N, Bauer WM, Krausgruber T, Goh I. Single-cell analysis reveals innate lymphoid cell lineage infidelity in atopic dermatitis. J Allergy Clin Immunol. 2022;149(2):624–639. doi:10.1016/j.jaci.2021.07.025

34. Čelakovská J, Čermáková E, Boudkova P, et al. Evaluation of innate lymphoid cells and their subsets in atopic dermatitis patients with and without dupilumab therapy. J DermatolTreat. 2024;35(1):2299721. doi:10.1080/09546634.2023.2299721

35. Ospelnikova T, Gevorkyan O, Mironov T, Andreeva S, Kolodyazhnaya L, Ershov F. Features of interferon and cytokine status in atopic dermatitis. Arch Asthma, Allergy Immunol. 2017;1:009–014. doi:10.29328/journal.haard.1001002

36. Karmon M, Kopel E, Barzilai A, et al. Altered RNA editing in atopic dermatitis highlights the role of double-stranded RNA for immune surveillance. J Invest Dermatol. 2023;143(6):933–943.e8. doi:10.1016/j.jid.2022.11.010

37. Mack MR, Brestoff JR, Berrien-Elliott MM, et al. Blood natural killer cell deficiency reveals an immunotherapy strategy for atopic dermatitis. Sci Transl Med. 2020;12(532):eaay1005. doi:10.1126/scitranslmed.aay1005

38. Möbus L, Rodriguez E, Harder I, et al. Elevated NK-cell transcriptional signature and dysbalance of resting and activated NK cells in atopic dermatitis. J Allergy Clin Immunol. 2021;147(5):1959–1965.e2. doi:10.1016/j.jaci.2020.11.022

39. Wang Y, Wu Y, Gu C, et al. Peripheral blood mononuclear cell- transcriptome signatures of atopic dermatitis and prediction for the efficacy of dupilumab. J Dermatol Sci. 2023;111(3):83–92. doi:10.1016/j.jdermsci.2023.06.002

40. Worm M, Glatzel V, Baumgart S, et al. Immune cell profiling reveals natural killer and T cell subpopulations to be associated with atopic dermatitis severity. Clin Exp Allergy. 2023;53:105–108. doi:10.1111/cea.14228

41. Bai W, Yang L, Qiu J, et al. Single-cell analysis of CD4+ tissue residency memory cells (TRMs) in adult atopic dermatitis: a new potential mechanism. Genomics. 2024;116(4):110870. doi:10.1016/j.ygeno.2024.110870

42. Luo Y, Fang X, Zhou Y, et al. Senescent fibroblasts and innate immune cell activation might play a role in the pathogenesis of elderly atopic dermatitis. J Dermatol Sci. 2024;114(3):94–103. doi:10.1016/j.jdermsci.2024.04.002

43. de Lima JF, Teixeira FME, Ramos YÁL, et al. Outlining the skin-homing and circulating CLA+NK cells in patients with severe atopic dermatitis. Sci Rep. 2024;14(1):1–9. doi:10.1038/s41598-024-53224-8

44. Ochayon DE, Devore SB, Chang WC, et al. Progressive accumulation of hyperinflammatory NKG2D low NK cells in early childhood severe atopic dermatitis. Sci Immunol. 2024;9:eadd3085. doi:10.1126/sciimmunol.add3085

45. Totsuka A, Omori-Miyake M, Kawashima M, Yagi J, Tsunemi Y. Expression of keratin 1, keratin 10, desmoglein 1 and desmocollin 1 in the epidermis: possible downregulation by interleukin-4 and interleukin-13 in atopic dermatitis. Eur J Dermatol. 2017;27(3):247–253. doi:10.1684/ejd.2017.2985

46. Tsoi LC, Rodriguez E, Degenhardt F, et al. Atopic dermatitis is an il-13–dominant disease with greater molecular heterogeneity compared to psoriasis. J Invest Dermatol. 2019;139(7):1480–1489. doi:10.1016/j.jid.2018.12.018

47. Wang S, Zhu R, Gu C, et al. Distinct clinical features and serum cytokine pattern of elderly atopic dermatitis in China. J Eur Acad Dermatol Venereol. 2020;34(10):2346–2352. doi:10.1111/jdv.16346

48. Rojahn TB, Vorstandlechner V, Krausgruber T, et al. Single-cell transcriptomics combined with interstitial fluid proteomics defines cell type–specific immune regulation in atopic dermatitis. J Allergy Clin Immunol. 2020;146(5):1056–1069. doi:10.1016/j.jaci.2020.03.041

49. Acevedo N, Benfeitas R, Katayama S, et al. Epigenetic alterations in skin homing CD4+CLA+ T cells of atopic dermatitis patients. Sci Rep. 2020;10(1):1–18. doi:10.1038/s41598-020-74798-z

50. Miranda E, Roberts J, Novick S, et al. Immunohistochemical characterization of the il-13_il-4 receptor α axis in the skin of adult patients with moderate to severe atopic dermatitis and healthy controls. J Invest Dermatol. 2021;141:440–443. doi:10.1016/j.jid.2020.05.108

51. Alkon N, Assen FP, Arnoldner T, et al. Single-cell RNA sequencing defines disease-specific differences between chronic nodular prurigo and atopic dermatitis. J Allergy Clin Immunol. 2023;152(2):420–435. doi:10.1016/j.jaci.2023.04.019

52. Xuan Z, Chen X, Zhou W. Exploring causal correlations between circulating cytokines and atopic dermatitis: a bidirectional two-sample Mendelian randomization study. Front Immunol. 2024;15:1367958. doi:10.3389/fimmu.2024.1367958

53. Wiegmann H, Renkhold L, Zeidler C, Agelopoulos K, Ständer S. Interleukin profiling in atopic dermatitis and chronic nodular prurigo. Int J Mol Sci. 2024;25:8445.

54. Czarnowicki T, Gonzalez J, Shemer A, et al. Severe atopic dermatitis is characterized by selective expansion of circulating TH2/TC2 and TH22/TC22, but not TH17/TC17, cells within the skin-homing T-cell population. J Allergy Clin Immunol. 2015;136(1):104–115.e7. doi:10.1016/j.jaci.2015.01.020

55. Noda S, Suárez-Fariñas M, Ungar B, et al. The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization. J Allergy Clin Immunol. 2015;136(5):1254–1264. doi:10.1016/j.jaci.2015.08.015

56. Mobus L, Rodriguez E, Harder I, et al. Atopic dermatitis displays stable and dynamic skin transcriptome signatures. J Allergy Clin Immunol. 2021;147(1):213–223. doi:10.1016/j.jaci.2020.06.012

57. Wu Y, Gu C, Wang S, et al. Serum biomarker-based endotypes of atopic dermatitis in China and prediction for efficacy of dupilumab. Br J Dermatol. 2023;188:649–660. doi:10.1093/bjd/ljad032

58. Del Duca E, Renert-Yuval Y, Pavel AB, et al. Proteomic characterization of atopic dermatitis blood from infancy to adulthood. J Am Acad Dermatol. 2023;88(5):1083–1093. doi:10.1016/j.jaad.2022.12.050

59. Facheris P, Da Rosa JC, Pagan AD, et al. Age of onset defines two distinct profiles of atopic dermatitis in adults. Allergy. 2023;78:2202–2214. doi:10.1111/all.15741

60. Brunner PM, Suárez-Fariñas M, He H, et al. The atopic dermatitis blood signature is characterized by increases in inflammatory and cardiovascular risk proteins. Sci Rep. 2017;7:8707. doi:10.1038/s41598-017-09207-z

61. Sanyal RD, Pavel AB, Glickman J, et al. Atopic dermatitis in African American patients is T H 2/T H 22-skewed with T H 1/T H 17 attenuation. Ann Allergy Asthma Immunol. 2019;122:99–110. doi:10.1016/j.anai.2018.08.024

62. Brunner PM, Israel A, Zhang N, et al. Early-onset pediatric atopic dermatitis is characterized by TH2/TH17/TH22-centered inflammation and lipid alterations. J Allergy Clin Immunol. 2018;141(6):2094–2106. doi:10.1016/j.jaci.2018.02.040

63. Pavel AB, Zhou L, Diaz A, et al. The proteomic skin profile of moderate-to-severe atopic dermatitis patients shows an inflammatory signature. J Am Acad Dermatol. 2020;82(3):690–699. doi:10.1016/j.jaad.2019.10.039

64. Tsoi LC, Rodriguez E, Stölzl D, et al. Progression of acute-to-chronic atopic dermatitis is associated with quantitative rather than qualitative changes in cytokine responses. J Allergy Clin Immunol. 2020;145(5):1406–1415. doi:10.1016/j.jaci.2019.11.047

65. Czarnowicki T, He H, Canter T, et al. Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood. J Allergy Clin Immunol. 2020;145(1):215–228. doi:10.1016/j.jaci.2019.09.031

66. Renert-yuval Y, Duca D, Pavel AB, Fang M, Lefferdink R. The molecular features of normal and atopic dermatitis skin in infants, children, adolescents, and adults. J Allergy Clin Immunol. 2021;148(1):148–163. doi:10.1016/j.jaci.2021.01.001

67. Pavel AB, Renert-Yuval Y, Wu J, et al. Tape strips from early-onset pediatric atopic dermatitis highlight disease abnormalities in nonlesional skin. Allergy Eur J Allergy Clin Immunol. 2021;76(1):314–325. doi:10.1111/all.14490

68. Rathore APS, St John AL. Immune responses to dengue virus in the skin. Open Biol. 2018;8:180087. doi:10.1098/rsob.180087

69. Cruz-Oliveira C, Freire JM, Conceição TM, Higa LM, Castanho MARB, Da Poian AT. Receptors and routes of dengue virus entry into the host cells. FEMS Microbiol Rev. 2015;39(2):155–170. doi:10.1093/femsre/fuu004

70. Lo YL, Liou GG, Lyu JH, Hsiao M, Hsu TL, Wong CH. Dengue virus infection is through a cooperative interaction between a mannose receptor and CLEC5A on macrophage as a multivalent hetero-complex. PLoS One. 2016;11(11):e0166474. doi:10.1371/journal.pone.0166474

71. van Leur SW, Heunis T, Munnur D, Sanyal S. Pathogenesis and virulence of flavivirus infections. Virulence. 2021;12(1):2814–2838. doi:10.1080/21505594.2021.1996059

72. Sprokholt J, Helgers LC, Geijtenbeek TBH. Innate immune receptors drive dengue virus immune activation and disease. Future Virol. 2018;13(4):287–305. doi:10.2217/fvl-2017-0146

73. Aguilar-Briseño JA, Moser J, Rodenhuis-Zybert IA. Understanding immunopathology of severe dengue: lessons learnt from sepsis. Curr Opin Virol. 2020;43:41–49. doi:10.1016/j.coviro.2020.07.010

74. Mathew A. Defining the role of NK cells during dengue virus infection. Immunology. 2018;154(4):557–562. doi:10.1111/imm.12928

75. Lee MF, Voon GZ, Lim HX, Chua ML, Poh CL. Innate and adaptive immune evasion by dengue virus. Front Cell Infect Microbiol. 2022;12:1004608. doi:10.3389/fcimb.2022.1004608

76. Toriyama M, Rizaldy D, Nakamura M, et al. Dendritic cell proliferation by primary cilium in atopic dermatitis. Front Mol Biosci. 2023;10:1149828. doi:10.3389/fmolb.2023.1149828

77. Wan SW, Wu-hsieh BA, Lin YS, Chen WY, Huang Y, Anderson R. The monocyte-macrophage-mast cell axis in dengue pathogenesis. J Biomed Sci. 2018;25:77. doi:10.1186/s12929-018-0482-9

78. Yang G, Seok JK, Kang HC, Cho YY, Lee HS, Lee JY. Skin barrier abnormalities and immune dysfunction in atopic dermatitis. Int J Mol Sci. 2020;21(8):2867. doi:10.3390/ijms21082867

79. Moosbrugger-Martinz V, Leprince C, Méchin MC, et al. Revisiting the roles of filaggrin in atopic dermatitis. Int J Mol Sci. 2022;23(10):5318. doi:10.3390/ijms23105318

80. Yazici D, Ogulur I, Kucukkase O, et al. Epithelial barrier hypothesis and the development of allergic and autoimmune diseases. Allergo J Int. 2022;31(4):91–102. doi:10.1007/s40629-022-00211-y

81. Nakajima S, Tie D, Nomura T, Kabashima K. Cytokine novel pathogenesis of atopic dermatitis from the view of cytokines in mice and humans. Cytokine. 2021;148:155664. doi:10.1016/j.cyto.2021.155664

82. Xiao C, Zhu Z, Zhang C, et al. A population of dermal Langerin+ dendritic cells promote the inflammation in mouse model of atopic dermatitis. Front Immunol. 2022;13:981819. doi:10.3389/fimmu.2022.981819

83. Tsai CM, Tsai CK, Cheng FJ, Chang CH, Yu HR. Allergic rhinitis and asthma rather than atopic dermatitis is a protective factor for dengue fever –– a nationwide population: a case-control study. Pediatr Respirol Crit Care Med. 2022;6(2):39–44. doi:10.4103/prcm.prcm

84. Yu HR, Tsai JH, Richard Lin CH, et al. Is asthma a protective factor for dengue fever? In vitro experiment and nationwide population-based cohort analysis. Allergol Int. 2019;68(4):486–493. doi:10.1016/j.alit.2019.06.001

85. Huang HJ, Lin YL, Liu CF, Kao HF, Wang JY. Mite allergen decreases DC-SIGN expression and modulates human dendritic cell differentiation and function in allergic asthma. Mucosal Immunol. 2011;4(5):519–527. doi:10.1038/mi.2011.17

86. Sherif NA, Ghozy S, Zayan AH, Elkady AH. Mast cell mediators in relation to dengue severity: a systematic review and meta-analysis. Rev Med Virol. 2020; 30:e2084. doi:10.1002/rmv.2084

87. Troupin A, Shirley D, Londono-renteria B, et al. A role for human skin mast cells in dengue virus infection and systemic spread. J Immunol. 2017;197(11):4382–4391. doi:10.4049/jimmunol.1600846

88. Syenina A, Saron WAA, Jagaraj CJ, et al. Th1-polarized, dengue virus-activated human mast cells induce endothelial transcriptional activation and permeability. Viruses. 2020;12:1379. doi:10.3390/v12121379

89. Keith YH, Egawa G, Honda T, Kabashima K. Mast cells in type 2 skin inflammation: maintenance and function. Eur J Immunol. 2023;53(8):2250359. doi:10.1002/eji.202250359

90. Sehra S, Serezani APM, Ocaña JA, Travers JB, Kaplan MH. Mast cells regulate epidermal barrier function and the development of allergic skin inflammation. J Invest Dermatol. 2016;136(7):1429–1437. doi:10.1016/j.jid.2016.03.019

91. Numata T, Harada K, Nakae S. Roles of mast cells in cutaneous diseases. Front Immunol. 2022;13:923495. doi:10.3389/fimmu.2022.923495

92. Voss M, Kotrba J, Gaffal E, Katsoulis-dimitriou K, Dudeck A. Mast cells in the skin: defenders of integrity or offenders in inflammation ? Int J Mol Sci. 2021;22:4589.

93. Droitcourt C, Vittrup I, Kerbrat S, Egeberg A, Thyssen JP. Risk of systemic infections in adults with atopic dermatitis: a nationwide cohort study. J Am Acad Dermatol. 2021;84(2):290–299. doi:10.1016/j.jaad.2020.07.111

94. Pingen M, Bryden SR, Pondeville E, et al. Host inflammatory response to mosquito bites enhances the severity of arbovirus infection. Immunity. 2016;44(6):1455–1469. doi:10.1016/j.immuni.2016.06.002

95. Yu S, Ge H, Li S, Qiu HJ. Modulation of macrophage polarization by viruses: turning off / on host antiviral responses. Front Microbiol. 2022;13:839585. doi:10.3389/fmicb.2022.839585

96. Herrant M, Loucoubar C, Boufkhed S, et al. Risk factors associated with asthma, atopic dermatitis and rhinoconjunctivitis in a rural Senegalese cohort. Allergy, Asthma Clin Immunol. 2015;11:24. doi:10.1186/s13223-015-0090-0

97. Sari IP, Thaha MA, Kurniawati Y, Tjekyan RMS. Hubungan hasil uji tusuk kulit alergen nyamuk terhadap keparahan klinis dermatitis atopik di RSUP Dr. Mohammad Hoesin Palembang [The relationship between mosquito allergen skin prick test results and clinical severity of atopic dermatitis at Dr. Mohammad Hoesin General Hospital, Palembang] MKS. 2014;46(2):95–103. Indonesian. doi:10.36706/mks.v46i2.2689

98. Conway MJ. Type I hypersensitivity promotes Aedes aegypti blood feeding. Sci Rep. 2021;11:14891. doi:10.1038/s41598-021-94416-w

99. Seneviratne J. Pathogenesis of atopic dermatitis: current concepts. J Ski Sex Transm Dis. 2021;3(2):113–117. doi:10.25259/JSSTD_8_2021

100. Lebre MC, van Capel TMM, Bos JD, Knol EF, Kapsenberg ML, de Jong EC. Aberrant function of peripheral blood myeloid and plasmacytoid dendritic cells in atopic dermatitis patients. J Allergy Clin Immunol. 2008;122(5):969–976. doi:10.1016/j.jaci.2008.08.028

101. Luci C, Gaudy-Marqueste C, Rouzaire P, et al. Peripheral natural killer cells exhibit qualitative and quantitative changes in patients with psoriasis and atopic dermatitis. Br J Dermatol. 2012;166(4):789–796. doi:10.1111/j.1365-2133.2012.10814.x

102. Sun P, Williams M, Nagabhushana N, Jani V, Defang G, Morrison BJ. NK cells activated through antibody-dependent cell cytotoxicity and armed with degranulation/ifn-γ production suppress antibody-dependent enhancement of dengue viral infection. Sci Rep. 2019;9(1):1109. doi:10.1038/s41598-018-36972-2

103. Quintino-De-Carvalho IL, Gonçalves-Pereira MH, Faria Ramos M, et al. Type 1 innate lymphoid cell and natural killer cells are sources of interferon-γ and other inflammatory cytokines associated with distinct clinical presentation in early dengue infection. J Infect Dis. 2022;225(1):84–93. doi:10.1093/infdis/jiab312

104. Zimmer CL, Cornillet M, Solà-Riera C, et al. NK cells are activated and primed for skin-homing during acute dengue virus infection in humans. Nat Commun. 2019;10(1):3897. doi:10.1038/s41467-019-11878-3

105. Shabrish S, Karnik N, Gupta V, Bhate P, Madkaikar M. Impaired NK cell activation during acute dengue virus infection: a contributing factor to disease severity. Heliyon. 2020;6(7):e04320. doi:10.1016/j.heliyon.2020.e04320

106. Vuong NL, Cheung KW, Periaswamy B, et al. Hyperinflammatory syndrome, natural killer cell function, and genetic polymorphisms in the pathogenesis of severe dengue. J Infect Dis. 2022;226(8):1338–1347. doi:10.1093/infdis/jiac093

107. King CA, Wegman AD, Endy TP. Mobilization and activation of the innate immune response to dengue virus. Front Cell Infect Microbiol. 2020;10:574417. doi:10.3389/fcimb.2020.574417

108. Malavige GN, Ogg GS. Pathogenesis of vascular leak in dengue virus infection. Immunology. 2017;151:261–269. doi:10.1111/imm.12748

109. Butcher MJ, Zhu J. Recent advances in understanding the Th1/Th2 effector choice. Fac Rev. 2021;10:30. doi:10.12703/r/10-30

110. Szymański Ł, Cios A, Ciepielak M, Stankiewicz W. Cytokines and apoptosis in atopic dermatitis. Adv Dermatol Allergol. 2021;XXXVIII(1):1–13. doi:10.5114/ada.2019.88394

111. Alsabbagh M, Ismaeel A. The role of cytokines in atopic dermatitis: a breakthrough in immunopathogenesis and treatment. Acta Dermatovenerol Alp Pannonica Adriat. 2022;31:13–31. doi:10.15570/actaapa.2022.3

112. Facheris P, Jeffery J, Del Duca E, Guttman-yassky E. The translational revolution in atopic dermatitis: the paradigm shift from pathogenesis to treatment. Cell Mol Immunol. 2023;20:448–474. doi:10.1038/s41423-023-00992-4

113. Furue M, Ulzii D, Vu YH, Tsuji G, Kido- M. Pathogenesis of Atopic Dermatitis: current Paradigm. Iran J Immunol. 2019;16(2):97–107. doi:10.22034/iji.2019.80253

114. Kale D, Kumar A, Chandra G, et al. Th2-predominant immune response underlies the pathogenesis of Dengue. Cytokine. 2024;177:156562. doi:10.1016/j.cyto.2024.156562

115. Chen RF, Liu JW, Yeh WT, et al. Altered T helper 1 reaction but not increase of virus load in patients with dengue hemorrhagic fever. FEMS Immunol Med Microbiol. 2005;44:43–50. doi:10.1016/j.femsim.2004.11.012

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