Work

Identification of an IL-27/osteopontin axis in dendritic cells and its modulation by IFN-γ limits IL-17–mediated autoimmune inflammation

Year: 2010

Type: article

Abstract: Dendritic cells (DCs) play a central role in determining the induction of T cell responses. IL-27 production by DCs favors induction of IL-10-producing regulatory T cells, whereas osteopontin (OPN) promotes pathogenic IL-17 T cell responses. The regulatory mechanisms in DCs that control these two cells types are not understood well. Here, we show that IFN-gamma induces IL-27 while inhibiting OPN expression in DCs both in vitro and in vivo and that engagement of IFN-gammaR expressed by DCs leads to suppression of IL-17 production while inducing IL-10 from T cells. DCs modified by IFN-gamma acquire IL-27-dependent regulatory function, promote IL-10-mediated T cell tolerance, and suppress autoimmune inflammation. Thus, our results identify a previously unknown pathway by which IFN-gamma limits IL-17-mediated autoimmune inflammation through differential regulation of OPN and IL-27 expression in DCs.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.1002099107

Authors: Gopal Murugaiyan, Akanksha Mittal, Howard L. Weiner

Institutions: Brigham and Women's Hospital, Harvard University, Weizmann Institute of Science

Language: English

Topic: T-cell and B-cell Immunology

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Multiple Sclerosis Society, National Institutes of Health, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke