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PMID: 16200068 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17.

Nature immunology ·Vol. 6 ·No. 11 ·2005-11-00 ·Pages 1133-41

Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, Wang Y, Hood L, Zhu Z, Tian Q, Dong C

Abstract

Interleukin 17 (IL-17) has been linked to autoimmune diseases, although its regulation and function have remained unclear. Here we have evaluated in vitro and in vivo the requirements for the differentiation of naive CD4 T cells into effector T helper cells that produce IL-17. This process required the costimulatory molecules CD28 and ICOS but was independent of the cytokines and transcription factors required for T helper type 1 or type 2 differentiation. Furthermore, both IL-4 and interferon-gamma negatively regulated T helper cell production of IL-17 in the effector phase. In vivo, antibody to IL-17 inhibited chemokine expression in the brain during experimental autoimmune encephalomyelitis, whereas overexpression of IL-17 in lung epithelium caused chemokine production and leukocyte infiltration. Thus, IL-17 expression characterizes a unique T helper lineage that regulates tissue inflammation.

MeSH Terms
Animals Antigens, Differentiation, T-Lymphocyte/genetics,metabolism CD28 Antigens/genetics,metabolism CD4-Positive T-Lymphocytes/cytology,immunology Cell Differentiation/genetics Cell Lineage Chemokines/genetics,metabolism Gene Expression Regulation Inducible T-Cell Co-Stimulator Protein Inflammation/genetics,immunology Interleukin-17/biosynthesis,genetics Lung/pathology Mice Mice, Transgenic Mutation Pneumonia/genetics,immunology,pathology Rats T-Lymphocytes, Helper-Inducer/cytology,immunology
Chemicals
Antigens, Differentiation, T-Lymphocyte CD28 Antigens Chemokines Icos protein, mouse Inducible T-Cell Co-Stimulator Protein Interleukin-17
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Park Heon
Department of Immunology, University of Washington, Seattle, Washington 98195, USA.
Li Zhaoxia
Yang Xuexian O
Chang Seon Hee
Nurieva Roza
Wang Yi-Hong
Wang Ying
Hood Leroy
Zhu Zhou
Tian Qiang
Dong Chen
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Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2908
DOI
10.1038/ni1261
Published
2005-11-00
Epub
2005-00-02
Pages
1133-41
Language
English
Region
United States
NLM ID
100941354
PMCID
PMC1618871
Subset
IM
Grants
NIAID NIH HHS · R01 AI050746 · United States
NIAID NIH HHS · R01 AI050761 · United States
NIAMS NIH HHS · R01 AR050772 · United States
Corrections
CommentIn
PMID: 16239919
External Links
PubMed source DOI: 10.1038/ni1261 PMC Full Text View journal details
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