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* Department of Pediatrics, Herman B. Wells Center for Pediatric Research,
Department of Microbiology and Immunology, and Walther Cancer Institute, Indiana University School of Medicine, Indianapolis, IN 46202;
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, IL 60611; and
Department of Pathology and Microbiology, New York University School of Medicine, New York, NY 10016
IL-17-secreting CD4+ T cells are critically involved in inflammatory immune responses. Development of these cells is promoted in vivo and in vitro by IL-23 or TGF
1 plus IL-6. Despite growing interest in this inflammatory Th subset, little is known about the transcription factors that are required for their development. We demonstrate that Stat3 is required for programming the TGF1 plus IL-6 and IL-23-stimulated IL-17-secreting phenotype, as well as for ROR
t expression in TGF1 plus IL-6-primed cells. Moreover, retroviral transduction of a constitutively active Stat3 into differentiating T cell cultures enhances IL-17 production from these cells. We further show that Stat4 is partially required for the development of IL-23-, but not TGF1 plus IL-6-primed IL-17-secreting cells, and is absolutely required for IL-17 production in response to IL-23 plus IL-18. The requirements for Stat3 and Stat4 in the development of these IL-17-secreting subsets reveal additional mechanisms in Th cell fate decisions during the generation of proinflammatory cell types.
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 AI45515 (to M.H.K.) and AI50837 (to G.S.K.). A.N.M. and D.G.Z. are Predoctoral Fellows of the American Heart Association.
2 A.N.M. and H.-C.C. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Mark H. Kaplan, Department of Pediatrics, Indiana University School of Medicine, HB Wells Center for Pediatric Research, 702 Barnhill Drive RI2600, Indianapolis, IN 46202. E-mail address: mkaplan2{at}iupui.edu
4 Abbreviation used in this paper: WT, wild type.
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