2. Academic Validation
  3. An Interleukin-25-Mediated Autoregulatory Circuit in Keratinocytes Plays a Pivotal Role in Psoriatic Skin Inflammation

An Interleukin-25-Mediated Autoregulatory Circuit in Keratinocytes Plays a Pivotal Role in Psoriatic Skin Inflammation

  • Immunity. 2018 Apr 17;48(4):787-798.e4. doi: 10.1016/j.immuni.2018.03.019.
Miao Xu 1,  Huiping Lu 2,  Young-Hee Lee 3,  Yelin Wu 4,  Kewei Liu 4,  Yuling Shi 5,  Haoran An 6,  Jingren Zhang 6,  Xiaohu Wang 2,  Yuping Lai 4,  Chen Dong 7
Affiliations

Affiliations

  • 1 Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China; Tsinghua University-Peking University Joint Center for Life Sciences, Beijing 100084, China.
  • 2 Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China.
  • 3 Department of Immunology and Center for Inflammation and Cancer, MD Anderson Cancer Center, Houston, TX 77054, USA.
  • 4 Shanghai Key Laboratory of Regulatory Biology, School of Life sciences, East China Normal University, Shanghai 200241, China.
  • 5 Department of Dermatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
  • 6 Center for Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.
  • 7 Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China; Beijing Key Lab for Immunological Research on Chronic Diseases, Beijing 100084, China. Electronic address: chendong@tsinghua.edu.cn.
PMID: 29653697 DOI: 10.1016/j.immuni.2018.03.019
Abstract

Psoriasis is a chronic autoinflammatory skin disease. Although interleukin-17, derived from lymphocytes, has been shown to be critical in psoriasis, the initiation and maintenance of chronic skin inflammation has not been well understood. IL-25 (also called IL-17E), another IL-17 family cytokine, is well known to regulate allergic responses and type 2 immunity. Here we have shown that IL-25, also highly expressed in the lesional skin of psoriasis patients, was regulated by IL-17 in murine skin of a imiquimod (IMQ)-induced psoriasis model. IL-25 injection induced skin inflammation, whereas germline or keratinocyte-specific deletion of IL-25 caused resistance to IMQ-induced psoriasis. Via IL-17RB expression in keratinocytes, IL-25 stimulated the proliferation of keratinocytes and induced the production of inflammatory cytokines and chemokines, via activation of the STAT3 transcription factor. Thus, our data demonstrate that an IL-17-induced autoregulatory circuit in keratinocytes is mediated by IL-25 and suggest that this circuit could be targeted in the treatment of psoriasis patients.

Keywords

IL-25; cytokines; keratinocytes; psoriasis.

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