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Review
. 2024 May;144(5):954-968.
doi: 10.1016/j.jid.2023.10.019. Epub 2023 Dec 11.

Genetic and Immunological Pathogenesis of Atopic Dermatitis

Charles F Schuler 4th  1 , Lam C Tsoi  2 , Allison C Billi  3 , Paul W Harms  4 , Stephan Weidinger  5 , Johann E Gudjonsson  6
Affiliations
Review

Genetic and Immunological Pathogenesis of Atopic Dermatitis

Charles F Schuler 4th et al. J Invest Dermatol. 2024 May.

Abstract

Type 2 immune-mediated diseases give a clear answer to the issue of nature (genetics) versus nurture (environment). Both genetics and environment play vital complementary roles in the development of atopic dermatitis (AD). As a key component of the atopic march, AD demonstrates the interactive nature of genetic and environmental contributions to atopy. From sequence variants in the epithelial barrier gene encoding FLG to the hygiene hypothesis, AD combines a broad array of contributions into a single syndrome. This review will focus on the genetic contribution to AD and where genetics facilitates the elicitation or enhancement of AD pathogenesis.

Keywords: Atopic dermatitis; Epidermal barrier; Epithelial barrier; GWAS; Genetics.

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Conflict of interest statement

JEG has had research support from Eli Lilly, AbbVie, Almirall, Prometheus, BMS, Janssen, Novartis, and Kyowa Kirin and served as an advisor to Sanofi, AbbVie, Almirall, BMS, Novartis, Eli Lilly, and Janssen. SW has received institutional research grants from Sanofi Deutschland GmbH, LEO Pharma, and Pfizer and performed consultancies and/or lectures for AbbVie, Almirall, Boehringer, Eli Lilly, Galderma, Kymab, Leo Pharma, Pfizer, Regeneron, and Sanofi. LCT has received support from Novartis, Janssen, and Galderma. The remaining authors state no conflict of interest.

Figures

Figure 1.
Figure 1.. Histological features of AD.
The common histological features of AD are shown in the acute, subacute, and chronic phases. Upper panel: global views of these features are shown. Lower panel: the specific status of various features (spongiosis, spongiotic vesiculation, etc) are shown in each stage of chronicity. Open circles indicate a lack of that feature at that time point. AD, atopic dermatitis.
Figure 2.
Figure 2.. Intersection of GWAS results and AD pathogenesis.
The pathogenesis of AD is shown here. Attention is given to the role of the skin barrier, innate and adaptive immunity, major cytokines, pruritus, and precipitants of AD. Note that all features of this figure with a GWAS association in AD, whether protective or predisposing, are called out in the figure as a lightning mark. Image was created with BioRender.com. AD, atopic dermatitis; DC, dendritic cell; ILC2, type 2 innate lymphoid cell, LC, Langerhans cell; MC, mast cell; Th2, T helper 2.
Figure 3.
Figure 3.. Cytokine networks of AD.
The connection between various cytokines and their effects in AD is depicted here in detail. Note that GWAS-level associations are shown as italicized genes in blue boxes in proximity to processes they affect. Image was created with BioRender.com. AD, atopic dermatitis; DC, dendritic cell; ILC2, type 2 innate lymphoid cell; LC, Langerhans cell; MC, mast cell; STAT, signal transducer and activator of transcription; Th2, T helper 2.
Figure 4.
Figure 4.. Linking novel treatments and genetics of AD.
Therapeutics for AD with mechanistic links to known GWAS-level associations in AD are shown. Image was created with BioRender.com. AD, atopic dermatitis; STAT, signal transducer and activator of transcription.
See this image and copyright information in PMC

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