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PMID: 21982596 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Pivotal role of dermal IL-17-producing γδ T cells in skin inflammation.

Immunity ·Vol. 35 ·No. 4 ·2011-10-28 ·Pages 596-610

Cai Y, Shen X, Ding C, Qi C, Li K, Li X, Jala VR, Zhang HG, Wang T, Zheng J, Yan J

Abstract

Interleukin-23 (IL-23) and CD4(+) T helper 17 (Th17) cells are thought to be critical in psoriasis pathogenesis. Here, we report that IL-23 predominantly stimulated dermal γδ T cells to produce IL-17 that led to disease progression. Dermal γδ T cells constitutively expressed the IL-23 receptor (IL-23R) and transcriptional factor RORγt. IL-17 production from dermal γδ T cells was independent of αβ T cells. The epidermal hyperplasia and inflammation induced by IL-23 were significantly decreased in T cell receptor δ-deficient (Tcrd(-/-)) and IL-17 receptor-deficient (Il17ra(-/-)) mice but occurred normally in Tcra(-/-) mice. Imiquimod-induced skin pathology was also significantly decreased in Tcrd(-/-) mice. Perhaps further promoting disease progression, IL-23 stimulated dermal γδ T cell expansion. In psoriasis patients, γδ T cells were greatly increased in affected skin and produced large amounts of IL-17. Thus, IL-23-responsive dermal γδ T cells are the major IL-17 producers in the skin and may represent a novel target for the treatment of psoriasis.

MeSH Terms
Animals Dermatitis/immunology,pathology Humans Interleukin-17/biosynthesis,immunology,metabolism Interleukin-23/biosynthesis,immunology Macrophages/immunology Mice Mice, Knockout Phenotype Psoriasis/immunology,pathology Receptors, Antigen, T-Cell, gamma-delta/deficiency,immunology Receptors, Interleukin-17/immunology T-Lymphocytes/immunology,metabolism
Chemicals
Interleukin-17 Interleukin-23 Receptors, Antigen, T-Cell, gamma-delta Receptors, Interleukin-17
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Cai Yihua
Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 20025, PR China.
Shen Xiaoyan
Ding Chuanlin
Qi Chunjian
Li Kejia
Li Xia
Jala Venkatakrishna R
Zhang Huang-ge
Wang Tian
Zheng Jie
Yan Jun
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2011.08.001
Published
2011-10-28
Epub
2011-00-06
Pages
596-610
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC3205267
Subset
IM
Grants
NCI NIH HHS · R01 CA086412-26 · United States
NCI NIH HHS · R01 CA150947-03 · United States
NCI NIH HHS · R01 CA150947 · United States
NCI NIH HHS · R01 CA086412 · United States
NCI NIH HHS · R01 CA150947-02 · United States
NCI NIH HHS · R01 CA150947-04 · United States
NCI NIH HHS · R01 CA150947-01 · United States
Corrections
ErratumIn
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CommentIn
PMID: 22051889
External Links
PubMed source DOI: 10.1016/j.immuni.2011.08.001 PMC Full Text View journal details
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