The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online
doi:10.1084/jem.20081712
The Journal of Experimental Medicine, Vol. 206, No. 3, 525-534
The Rockefeller University Press, 0022-1007 $30.00
© Kleinschek et al.
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 3750K)
Right arrow PDF+supp data (6389K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kleinschek, M. A.
Right arrow Articles by Kastelein, R. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kleinschek, M. A.
Right arrow Articles by Kastelein, R. A.
Related Collections
Right arrowRelated Article
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

BRIEF DEFINITIVE REPORT

 Circulating and gut-resident human Th17 cells express CD161 and promote intestinal inflammation

Melanie A. Kleinschek1, Katia Boniface1, Svetlana Sadekova2, Jeff Grein2, Erin E. Murphy2, Scott P. Turner2, Lisa Raskin2, Bela Desai2, William A. Faubion3, Rene de Waal Malefyt1, Robert H. Pierce2, Terrill McClanahan2, and Robert A. Kastelein1

1 Department of Immunology and 2 Department of Experimental Pathology and Pharmacology, Schering-Plough Biopharma, Palo Alto, CA 94304
3 Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905

CORRESPONDENCE Melanie A. Kleinschek: melanie.kleinschek{at}spcorp.com

The C-type lectin-like receptor CD161, which has recently been described to promote T cell expansion, is expressed on a discrete subset of human CD4 T cells. The function of such cells, however, has remained elusive. We now demonstrate that CD161+ CD4 T cells comprise a circulating and gut-resident T helper 17 (Th17) cell population. During Crohn's disease (CD), these CD161+ cells display an activated Th17 phenotype, as indicated by increased expression of interleukin (IL)-17, IL-22, and IL-23 receptor. CD161+ CD4 T cells from CD patients readily produce IL-17 and interferon {gamma} upon stimulation with IL-23, whereas, in healthy subjects, priming by additional inflammatory stimuli such as IL-1β was required to enable IL-23–induced cytokine release. Circulating CD161+ Th17 cells are imprinted for gut homing, as indicated by high levels of CC chemokine receptor 6 and integrin β7 expression. Supporting their colitogenic phenotype, CD161+ Th17 cells were found in increased numbers in the inflammatory infiltrate of CD lesions and induced expression of inflammatory mediators by intestinal cells. Our data identify CD161+ CD4 T cells as a resting Th17 pool that can be activated by IL-23 and mediate destructive tissue inflammation.

© 2009 Kleinschek et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?

Related Article

Flagging Th17 in Crohn's
Amy Maxmen
J. Exp. Med. 2009 206: 492-493. [Full Text] [PDF]



This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS