The Journal of Experimental Medicine
ELISpot, FluoroSpot and ELISA kits from Mabtech
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online
doi:10.1084/jem.20061738
The Journal of Experimental Medicine, Vol. 204, No. 1, 161-170
The Rockefeller University Press, 0022-1007 $30.00
© Kleinschek et al.
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 2853K)
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 Cua, D. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kleinschek, M. A.
Right arrow Articles by Cua, D. J.
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?

ARTICLE

 IL-25 regulates Th17 function in autoimmune inflammation

Melanie A. Kleinschek1, Alexander M. Owyang1, Barbara Joyce-Shaikh1, Claire L. Langrish1, Yi Chen1, Daniel M. Gorman1, Wendy M. Blumenschein2, Terrill McClanahan2, Frank Brombacher3, Stephen D. Hurst1, Robert A. Kastelein1, and Daniel J. Cua1

1 Discovery Research and 2 Experimental Pathology and Pharmacology, Schering-Plough Biopharma, Palo Alto, CA 94304
3 University of Cape Town, Rondebosch 7701, South Africa

CORRESPONDENCE Daniel J. Cua: daniel.cua{at}spcorp.com

Interleukin (IL)-25 is a member of the IL-17 family of cytokines. However, unlike the other members of this family, IL-25 promotes T helper (Th) 2 responses. We now show that IL-25 also regulates the development of autoimmune inflammation mediated by IL-17–producing T cells. We have generated IL-25–deficient (il25–/–) mice and found that they are highly susceptible to experimental autoimmune encephalomyelitis (EAE). The accelerated disease in the il25–/– mice is associated with an increase of IL-23 in the periphery and a subsequent increase in the number of inflammatory IL-17–, IFN{gamma}-, and TNF-producing T cells that invade the central nervous system. Neutralization of IL-17 but not IFN{gamma} in il25–/– mice prevented EAE, suggesting that IL-17 is a major disease-promoting factor. IL-25 treatment at several time points during a relapse-remitting model or chronic model of EAE completely suppressed disease. IL-25 treatment induced elevated production of IL-13, which is required for suppression of Th17 responses by direct inhibition of IL-23, IL-1ß, and IL-6 expression in activated dendritic cells. Thus, IL-25 and IL-17, being members of the same cytokine family, play opposing roles in the pathogenesis of organ-specific autoimmunity.

Abbreviations used: CNS, central nervous system; DLN, draining lymph node; EAE, experimental autoimmune encephalomyelitis; HR, homologous recombination; MOG, myelin oligodendrocyte glycoprotein; PTX, pertussis toxin; rAdV, replication-deficient adenoviral vector.

M.A. Kleinschek and A.M. Owyang contributed equally to this paper.

C.L. Langrish's present address is Roche Bioscience, Palo Alto, CA 94304.

S.D. Hurst's present address is Genentech, South San Francisco, CA 94080.


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?


This article has been cited by other articles:



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