| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
,
,,,
* Department of Gene and Cell Medicine and
Department of Surgery,
Immunology Institute, and
The Recanati/Miller Transplantation Institute, Mount Sinai School of Medicine, New York, NY 10029;
¶ Department of Surgery and Orthopaedics, Peking Union Medical College Hospital, Beijing, China;
|| Pathology and Microbiology, New York University School of Medicine, New York, NY 10016; and
# Unidad de Immunología de Trasplantes, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Madrid, Spain
IL-10 production by Th17 cells is critical for limiting autoimmunity and inflammatory responses. Gene array analysis on Stat6 and T-bet double-deficient Th17 cells identified the Th2 transcription factor c-Maf to be synergistically up-regulated by IL-6 plus TGFβ and associated with Th17 IL-10 production. Both c-Maf and IL-10 induction during Th17 polarization depended on Stat3, but not Stat6 or Stat1, and mechanistically differed from IL-10 regulation by Th2 or IL-27 signals. TGFβ was also synergistic with IL-27 to induce c-Maf, and it induced Stat1-independent IL-10 expression in contrast to IL-27 alone. Retroviral transduction of c-Maf was able to induce IL-10 expression in Stat6-deficient CD4 and CD8 T cells, and c-Maf directly transactivated IL-10 gene expression through binding to a MARE (Maf recognition element) motif in the IL-10 promoter. Taken together, these data reveal a novel role for c-Maf in regulating T effector development, and they suggest that TGFβ may antagonize Th17 immunity by IL-10 production through c-Maf induction.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grants R01 AI 62855 (to Y.D.) and AI 41428 (to J.S.B).
2 Address correspondence and reprint requests to Dr. Yaozhong Ding, Department of Gene and Cell Medicine, Box 1496, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, New York, NY 10029. E-mail address: yaozhong.ding{at}mssm.edu
3 Abbreviations used in this paper: KO, knockout; ChIP, chromatin immunoprecipitation; IL-10mt, mutated IL-10 promoter; IL-10wt, wild-type IL-10 promoter; MARE, Maf recognition element; ROR, retinoic acid-related orphan nuclear receptor.
This article has been cited by other articles:
|
|
 |
|
  C. Pot, H. Jin, A. Awasthi, S. M. Liu, C.-Y. Lai, R. Madan, A. H. Sharpe, C. L. Karp, S.-C. Miaw, I-C. Ho, et al. Cutting Edge: IL-27 Induces the Transcription Factor c-Maf, Cytokine IL-21, and the Costimulatory Receptor ICOS that Coordinately Act Together to Promote Differentiation of IL-10-Producing Tr1 Cells J. Immunol., July 15, 2009; 183(2): 797 - 801. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
