Ets1 suppresses atopic dermatitis by suppressing pathogenic T cell responses

Title
Ets1 suppresses atopic dermatitis by suppressing pathogenic T cell responses
Authors
이충구권호근강혜지김영남종희원영호박선희김태묵강근수루드라 디파얀전창덕박지용임신혁
Keywords
Immunology; Atopic dermatitis; CD4+ T cells; Th17/22; Ets1; IL6st
Issue Date
2019-03
Publisher
JCI Insight
Citation
VOL 4, NO 5-e124202-18
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.
URI
http://pubs.kist.re.kr/handle/201004/69160
ISSN
2379-3708
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KIST Publication > Article
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