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IL-27 Is a Key Regulator of IL-10 and IL-17 Production by Human CD4⁺ T Cells¹

Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115

Although the physiologic pathways that control regulatory T cells (Foxp3-expressing regulatory T cells, IL-10-secreting Tr1 cells) and Th17 cells in rodents have been defined, the factors that control these differentiation pathways in humans are not well understood. In this study, we show that IL-27 promotes the differentiation of IL-10-secreting Tr1 cells while inhibiting Th17 generation and molecules associated with Th17 function. Furthermore, IL-27 inhibits IL-17-polarizing cytokines on dendritic cells, which in turn decrease IL-17 secretion from T cells. Our results demonstrate that IL-27 plays a key role in human T cells by promoting IL-10-secreting Tr1 cells and inhibiting Th17 cells and thus provides a dual regulatory mechanism to control autoimmunity and tissue inflammation.

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 the National Institutes of Health Grants (NS038037, AI043458, and NS23132), the National MS Society, and the Nancy Davis Foundation. A.M. was supported by the National Research Service Award Fellowship (Grant F32AI075761) from the National Institute of Allergy and Infectious Diseases.

² Address correspondence and reprint requests to Dr. Howard L. Weiner, Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115. E-mail address: hweiner{at}rics.bwh.harvard.edu

³ Abbreviations used in this paper: Treg, regulatory T cell; DC, dendritic cell; PGN, peptidoglycan; RORC, retinoid orphan nuclear receptor (RORC), which encodes the human ortholog of mouse RORt.

⁴ The online version of this article contains supplemental material.