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This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0900735v1 183/8/4957    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by El-behi, M. Articles by Rostami, A. PubMed PubMed Citation Articles by El-behi, M. Articles by Rostami, A.

Differential Effect of IL-27 on Developing versus Committed Th17 Cells¹

Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107

IL-27 counters the effect of TGF-β+IL-6 on naive CD4⁺ T cells, resulting in near complete inhibition of de novo Th17 development. In contrast, little is known about the effect of IL-27 on already differentiated Th17 cells. A better understanding of how IL-27 regulates these cells is needed to evaluate the therapeutic potential of IL-27 in Th17 cells-associated diseases. In this study, we show that IL-27 had surprisingly little effect on committed Th17 cells, despite its expression of a functional IL-27R. Contrary to de novo differentiation of Th17 cells, IL-27 did not suppress expression of retinoid-related orphan receptor (ROR)t or ROR in committed Th17 cells. Consistent with this finding, the frequency of committed Th17 cells and their cytokine secretion remained unaffected by IL-27. Both memory Th17 cells (CD4⁺CD25^–CD62L^low) that developed in vivo and encephalitogenic Th17 cells infiltrating the CNS of mice developing experimental autoimmune encephalomyelitis produced similar amounts of IL-17A when reactivated with IL-23 in the absence and presence of exogenous IL-27. Finally, IL-27 failed to suppress encephalitogenicity of Th17 cells in an adoptive transfer of experimental autoimmune encephalomyelitis. Analysis ex vivo of transferred Th17 cells in the spleen and CNS of recipient mice showed that cells retained similar phenotype irrespective of whether cells were treated or not with IL-27. Our data demonstrate that in contrast to inhibition of de novo differentiation of Th17 cells, IL-27 has little or no effect on committed Th17 cells. These findings indicate that therapeutic applications of IL-27 might have a limited efficacy in inflammatory conditions where aggressive Th17 responses have already developed.

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 grants from the National Institutes of Health, the National Multiple Sclerosis Society (NMSS), and Common Wealth of Pennsylvania Department of Health (to A.R.).

² Address correspondence and reprint requests to Dr. Abdolmohamad Rostami, Department of Neurology, Thomas Jefferson University, Jefferson Hospital for Neuroscience Building, 900 Walnut Street, Philadelphia, PA 19107. E-mail address: a.m.rostami{at}jefferson.edu

³ Abbreviations used in this paper: DC, dendritic cell; EAE, experimental autoimmune encephalomyelitis; MOG, myelin oligodendrocyte glycoprotein; ROR, retinoid-related orphan receptor.

⁴ The online version of this article contains supplemental material.