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The Journal of Immunology, 2008, 181, 5948-5955
Copyright © 2008 by The American Association of Immunologists, Inc.

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IL-23 Promotes Maintenance but Not Commitment to the Th17 Lineage1

Gretta L. Stritesky2, Norman Yeh2 and Mark H. Kaplan3

Departments of Pediatrics, HB Wells Center for Pediatric Research and Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202

IL-23 plays a critical role establishing inflammatory immunity and enhancing IL-17 production in vivo. However, an understanding of how it performs those functions has been elusive. In this report, using an IL-17-capture technique, we demonstrate that IL-23 maintains the IL-17-secreting phenotype of purified IL-17+ cells without affecting cell expansion or survival. IL-23 maintains the Th17 phenotype over multiple rounds of in vitro stimulation most efficiently in conjunction with IL-1β. However, in contrast to Th1 and Th2 cells, the Th17 phenotype is not stable and when long-term IL-23-stimulated Th17 cultures are exposed to Th1- or Th2-inducing cytokines, the Th17 genetic program is repressed and cells that previously secreted IL-17 assume the cytokine secreting profile of other Th subsets. Thus, while IL-23 can maintain the Th17 phenotype, it does not promote commitment to an IL-17-secreting lineage.

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 U.S. Public Health Service Award AI45515 (to M.H.K.) from the National Institutes of Health. G.L.S. and N.Y. were supported by a Training Grant in Immunology and Infectious Disease (T32AI060519) and N.Y. was supported by the DeVault Fellowship from the Indiana University Cancer Biology Training Program.

2 G.L.S. and N.Y. contributed equally to this study.

3 Address correspondence and reprint requests to Dr. Mark H. Kaplan, Department of Pediatrics, and Microbiology and Immunology, Wells Center for Pediatric Research, Indiana University School of Medicine, 702 Barnhill Drive, RI 2600, Indianapolis, IN 46202. E-mail address: mkaplan2{at}iupui.edu

4 Abbreviations used in this paper: Treg, regulatory T cell.


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