Send to

Choose Destination
JCI Insight. 2019 Mar 7;4(5). pii: 124202. doi: 10.1172/jci.insight.124202. eCollection 2019 Mar 7.

Ets1 suppresses atopic dermatitis by suppressing pathogenic T cell responses.

Author information

Natural Product Informatics Research Center, Korea Institute of Science and Technology (KIST) Gangneung Institute of Natural Products, Gangneung, South Korea.
Academy of Immunology and Microbiology (AIM), Institute for Basic Science (IBS), Pohang, South Korea.
Department of Microbiology, College of Medicine, Yonsei University, Seoul, South Korea.
Department of Oral Pathology, School of Dentistry, Chonnam National University, Gwangju, South Korea.
Department of Pathology and.
Department of Dermatology, Chonnam National University Medical School, Gwangju, South Korea.
Department of Microbiology, Dankook University, Cheonan, South Korea.
Division of Integrative Biosciences and Biotechnology (IBB), Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, South Korea.
School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju, South Korea.


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.


Adaptive immunity; Allergy; Immunology; T cells

Free full text

Supplemental Content

Full text links

Icon for American Society for Clinical Investigation
Loading ...
Support Center