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PMID: 19448631 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A protective function for interleukin 17A in T cell-mediated intestinal inflammation.

Nature immunology ·Vol. 10 ·No. 6 ·2009-06-00 ·Pages 603-9

O'Connor W, Kamanaka M, Booth CJ, Town T, Nakae S, Iwakura Y, Kolls JK, Flavell RA

Abstract

Interleukin 23 (IL-23) and IL-17 have been linked to the pathogenesis of several chronic inflammatory disorders, including inflammatory bowel disease. Yet as an important function for IL-23 is emerging, the function of IL-17 in inflammatory bowel disease remains unclear. Here we demonstrate IL-17A-mediated protection in the CD45RBhi transfer model of colitis. An accelerated wasting disease elicited by T cells deficient in IL-17A correlated with higher expression of genes encoding T helper type 1-type cytokines in colon tissue. IL-17A also modulated T helper type 1 polarization in vitro. Furthermore, T cells deficient in the IL-17 receptor elicited an accelerated, aggressive wasting disease relative to that elicited by wild-type T cells in recipient mice. Our data demonstrate a protective function for IL-17 and identify T cells as not only the source but also a target of IL-17 in vivo.

MeSH Terms
Adoptive Transfer Animals Cell Differentiation Cell Proliferation Cells, Cultured Colitis/immunology Disease Models, Animal Gene Expression Profiling Interferon-gamma Interleukin-17/immunology,metabolism Leukocyte Common Antigens/metabolism Lymphocyte Activation Mice Mice, Inbred BALB C Mice, Knockout Receptors, Interleukin-17/immunology T-Box Domain Proteins/metabolism Th1 Cells/immunology Wasting Syndrome/immunology
Chemicals
Il17a protein, mouse Il17ra protein, mouse Interleukin-17 Receptors, Interleukin-17 T-Box Domain Proteins T-box transcription factor TBX21 Interferon-gamma Leukocyte Common Antigens
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
O'Connor William
Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.
Kamanaka Masahito
Booth Carmen J
Town Terrence
Nakae Susumu
Iwakura Yoichiro
Kolls Jay K
Flavell Richard A
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Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2916
DOI
10.1038/ni.1736
Published
2009-06-00
Pages
603-9
Language
English
Region
United States
NLM ID
100941354
PMCID
PMC2709990
Subset
IM
Grants
NHLBI NIH HHS · R37 HL079142 · United States
NIA NIH HHS · R00 AG029726-03 · United States
Howard Hughes Medical Institute · United States
NIA NIH HHS · R00 AG029726 · United States
NIA NIH HHS · R00 AG029726-02 · United States
Corrections
CommentIn
PMID: 19448657
External Links
PubMed source DOI: 10.1038/ni.1736 PMC Full Text View journal details
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