A protective function for interleukin 17a in t cell–mediated intestinal inflammation

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_. Access through your

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macrophages and polymorphonuclear leukocytes in Lyme carditis. _Infect. Immun._ 75, 613–620 (2007). Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS We thank G. Tokmoulina

for assistance with flow cytometry cell sorting; E. Esplugues for critical reading of the manuscript and comments; A. Lin for assistance with statistical analyses; and F. Manzo for

administrative assistance. Supported by the National Multiple Sclerosis Society (W.O.) and the Howard Hughes Medical Institute (R.A.F.). AUTHOR INFORMATION Author notes * Terrence Town

Present address: Present address: Department of Neurosurgery, Biomedical Sciences and Department of Medicine, Maxine Dunitz Neurosurgical Institute Cedars-Sinai Medical Center, Los Angeles,

California, USA., AUTHORS AND AFFILIATIONS * Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA William O'Connor Jr, Masahito Kamanaka, 

Terrence Town & Richard A Flavell * Section of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut, USA Carmen J Booth * Center for Experimental Medicine,

Institute of Medical Science, University of Tokyo, Tokyo, Japan Susumu Nakae & Yoichiro Iwakura * Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA Jay K Kolls *

Howard Hughes Medical Institute, Yale University, New Haven, Connecticut, USA Richard A Flavell Authors * William O'Connor Jr View author publications You can also search for this

author inPubMed Google Scholar * Masahito Kamanaka View author publications You can also search for this author inPubMed Google Scholar * Carmen J Booth View author publications You can also

search for this author inPubMed Google Scholar * Terrence Town View author publications You can also search for this author inPubMed Google Scholar * Susumu Nakae View author publications

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CONTRIBUTIONS W.O. and R.A.F. designed the study and wrote the manuscript; M.K. provided flow cytometry data, advice and technical guidance; W.O. did all other _in vitro_ and _in vivo_

experimental work; C.J.B. did histopathological scoring analyses; T.T. provided assistance with statistical analyses; Y.I. and S.N. provided _Il17a__−/−_ mice; and J.K.K. provided the

_Il17ra__−/−_ mice. CORRESPONDING AUTHOR Correspondence to Richard A Flavell. SUPPLEMENTARY INFORMATION SUPPLEMENTARY TEXT AND FIGURES Supplementary Figures 1–7 (PDF 2130 kb) RIGHTS AND

PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE O'Connor Jr, W., Kamanaka, M., Booth, C. _et al._ A protective function for interleukin 17A in T cell–mediated

intestinal inflammation. _Nat Immunol_ 10, 603–609 (2009). https://doi.org/10.1038/ni.1736 Download citation * Received: 20 February 2009 * Accepted: 14 April 2009 * Published: 17 May 2009 *

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