Genetic and Immunological Pathogenesis of Atopic Dermatitis

Overview

Journal J Invest Dermatol

Publisher Elsevier

Specialty Dermatology

Date 2023 Dec 12

PMID 38085213

Authors

Charles F Schuler 4th

Lam C Tsoi

Allison C Billi

Paul W Harms

Stephan Weidinger

Johann E Gudjonsson

Affiliations

Soon will be listed here.

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.

Citing Articles

Atopic dermatitis: pathogenesis and therapeutic intervention.

Yue C, Zhou H, Wang X, Yu J, Hu Y, Zhou P MedComm (2020). 2024; 5(12):e70029.

PMID: 39654684 PMC: 11625510. DOI: 10.1002/mco2.70029.

Update on the pathogenesis of atopic dermatitis.

Criado P, Miot H, Bueno-Filho R, Ianhez M, Criado R, Silva de Castro C An Bras Dermatol. 2024; 99(6):895-915.

PMID: 39138034 PMC: 11551276. DOI: 10.1016/j.abd.2024.06.001.

Multi-ancestry Genome-Wide Association Meta-Analysis Identifies Novel Loci in Atopic Dermatitis.

Oliva M, Sarkar M, March M, Saeidian A, Mentch F, Hsieh C medRxiv. 2024; .

PMID: 38946956 PMC: 11213042. DOI: 10.1101/2024.06.17.24308897.

References

Archer N, Jo J, Lee S, Kim D, Smith B, Ortines R . Injury, dysbiosis, and filaggrin deficiency drive skin inflammation through keratinocyte IL-1α release. J Allergy Clin Immunol. 2018; 143(4):1426-1443.e6. PMC: 6424655. DOI: 10.1016/j.jaci.2018.08.042. View

Al-Janabi A, Eyre S, Foulkes A, Khan A, Dand N, Burova E . Atopic Polygenic Risk Score Is Associated with Paradoxical Eczema Developing in Patients with Psoriasis Treated with Biologics. J Invest Dermatol. 2023; 143(8):1470-1478.e1. DOI: 10.1016/j.jid.2023.01.021. View

Weidinger S, Willis-Owen S, Kamatani Y, Baurecht H, Morar N, Liang L . A genome-wide association study of atopic dermatitis identifies loci with overlapping effects on asthma and psoriasis. Hum Mol Genet. 2013; 22(23):4841-56. PMC: 3820131. DOI: 10.1093/hmg/ddt317. View

Jabbar-Lopez Z, Craven J, Logan K, Greenblatt D, Marrs T, Radulovic S . Longitudinal analysis of the effect of water hardness on atopic eczema: evidence for gene-environment interaction. Br J Dermatol. 2019; 183(2):285-293. DOI: 10.1111/bjd.18597. View

Lowa A, Graff P, Kaessmeyer S, Hedtrich S . Fibroblasts from atopic dermatitis patients trigger inflammatory processes and hyperproliferation in human skin equivalents. J Eur Acad Dermatol Venereol. 2020; 34(6):e262-e265. DOI: 10.1111/jdv.16240. View

Novak N . An update on the role of human dendritic cells in patients with atopic dermatitis. J Allergy Clin Immunol. 2012; 129(4):879-86. DOI: 10.1016/j.jaci.2012.01.062. View

Papp K, Szepietowski J, Kircik L, Toth D, Eichenfield L, Leung D . Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: Results from 2 phase 3, randomized, double-blind studies. J Am Acad Dermatol. 2021; 85(4):863-872. DOI: 10.1016/j.jaad.2021.04.085. View

Cevikbas F, Wang X, Akiyama T, Kempkes C, Savinko T, Antal A . A sensory neuron-expressed IL-31 receptor mediates T helper cell-dependent itch: Involvement of TRPV1 and TRPA1. J Allergy Clin Immunol. 2013; 133(2):448-60. PMC: 3960328. DOI: 10.1016/j.jaci.2013.10.048. View

Margolis D, Kim B, Apter A, Gupta J, Hoffstad O, Papadopoulos M . Thymic stromal lymphopoietin variation, filaggrin loss of function, and the persistence of atopic dermatitis. JAMA Dermatol. 2014; 150(3):254-9. PMC: 4414492. DOI: 10.1001/jamadermatol.2013.7954. View

10.

Rosenbaum B, Klein R, Hagan P, Seadey M, Quarcoo N, Hoffmann R . Dermatology in Ghana: a retrospective review of skin disease at the Korle Bu Teaching Hospital Dermatology Clinic. Pan Afr Med J. 2017; 26:125. PMC: 5429409. DOI: 10.11604/pamj.2017.26.125.10954. View

11.

Paternoster L, Standl M, Waage J, Baurecht H, Hotze M, Strachan D . Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis. Nat Genet. 2015; 47(12):1449-1456. PMC: 4753676. DOI: 10.1038/ng.3424. View

12.

Bin L, Malley C, Taylor P, Boorgula M, Chavan S, Daya M . Whole genome sequencing identifies novel genetic mutations in patients with eczema herpeticum. Allergy. 2021; 76(8):2510-2523. PMC: 8978872. DOI: 10.1111/all.14762. View

13.

Cai X, Cheng L, Yu C, Wu Y, Fang L, Zheng X . GWAS Follow-up Study Discovers a Novel Genetic Signal on 10q21.2 for Atopic Dermatitis in Chinese Han Population. Front Genet. 2019; 10:174. PMC: 6422937. DOI: 10.3389/fgene.2019.00174. View

14.

Czarnowicki T, Kim H, Villani A, Glickman J, Del Duca E, Han J . High-dimensional analysis defines multicytokine T-cell subsets and supports a role for IL-21 in atopic dermatitis. Allergy. 2021; 76(10):3080-3093. DOI: 10.1111/all.14845. View

15.

Toshitani A, Ansel J, Chan S, Li S, Hanifin J . Increased interleukin 6 production by T cells derived from patients with atopic dermatitis. J Invest Dermatol. 1993; 100(3):299-304. DOI: 10.1111/1523-1747.ep12469875. View

16.

Salimi M, Barlow J, Saunders S, Xue L, Gutowska-Owsiak D, Wang X . A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis. J Exp Med. 2013; 210(13):2939-50. PMC: 3865470. DOI: 10.1084/jem.20130351. View

17.

Stevens M, Zhang Z, Johansson E, Ray S, Jagpal A, Ruff B . Disease-associated KIF3A variants alter gene methylation and expression impacting skin barrier and atopic dermatitis risk. Nat Commun. 2020; 11(1):4092. PMC: 7427989. DOI: 10.1038/s41467-020-17895-x. View

18.

Pellefigues C, Naidoo K, Mehta P, Schmidt A, Jagot F, Roussel E . Basophils promote barrier dysfunction and resolution in the atopic skin. J Allergy Clin Immunol. 2021; 148(3):799-812.e10. PMC: 8410897. DOI: 10.1016/j.jaci.2021.02.018. View

19.

Kang M, Lee S, Park Y, Kim B, Lee M, Kim J . Interactions Between Variants and in the Gut Contribute to the Development of Atopic Dermatitis in Infancy. Allergy Asthma Immunol Res. 2021; 13(3):404-419. PMC: 7984953. DOI: 10.4168/aair.2021.13.3.404. View

20.

Schuler 4th C, Gudjonsson J . IL-33 antagonism does not improve chronic atopic dermatitis: What can we learn?. J Allergy Clin Immunol. 2022; 150(6):1410-1411. PMC: 10087095. DOI: 10.1016/j.jaci.2022.10.009. View