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Ets1 suppresses atopic dermatitis by suppressing pathogenic T cell responses

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Title
Ets1 suppresses atopic dermatitis by suppressing pathogenic T cell responses
Author(s)
Choong-Gu Lee; Ho-Keun Kwon; Hyeji Kang; Young Kim; Jong Hee Nam; Young Ho Won; Sunhee Park; Taemook Kim; Keunsoo Kang; Dipayan Rudra; Chang-Duk Jun; Zee Yong Park; Sin-Hyeog Im
Publication Date
2019-03
Journal
JCI INSIGHT, v.4, no.5, pp.e124202 -
Publisher
AMER SOC CLINICAL INVESTIGATION INC
Abstract
Atopic dermatitis (AD) is a complex inflammatory skin disease mediated by immune cells of both adaptive and innate types. Among them, CD4+ Th cells are one of major players of AD pathogenesis. Although the pathogenic role of Th2 cells has been well characterized, Th17/Th22 cells are also implicated in the pathogenesis of AD. However, the molecular mechanisms underlying pathogenic immune responses in AD remain unclear. We sought to investigate how the defect in the AD susceptibility gene, Ets1, is involved in AD pathogenesis in human and mice and its clinical relevance in disease severity by identifying Ets1 target genes and binding partners. Consistent with the decrease in ETS1 levels in severe AD patients and the experimental AD-like skin inflammation model, T cell-specific Ets1-deficient mice (Ets1ΔdLck) developed severe AD-like symptoms with increased pathogenic Th cell responses. A T cell-intrinsic increase of gp130 expression upon Ets1 deficiency promotes the gp130-mediated IL-6 signaling pathway, thereby leading to the development of severe AD-like symptoms. Functional blocking of gp130 by selective inhibitor SC144 ameliorated the disease pathogenesis by reducing pathogenic Th cell responses. Our results reveal a protective role of Ets1 in restricting pathogenic Th cell responses and suggest a potential therapeutic target for AD treatment. Copyright 2019, American Society for Clinical Investigation.
URI
https://pr.ibs.re.kr/handle/8788114/6006
ISSN
2379-3708
Appears in Collections:
Academy of Immunology and Microbiology(면역 미생물 공생 연구단) > Journal Papers (저널논문)
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