Type I IFN promotes IL-10 production from T cells to suppress Th17 cells and Th17-associated autoimmune inflammation

• Published in: PloS one 2011-12, Vol.6 (12), p.e28432-e28432
• Main Authors: Zhang, Lixia, Yuan, Shunzong, Cheng, Genhong, Guo, Beichu
• Format: Article
• Language: English
• Subjects: Adoptive transfer; Alleles; Analysis; Animal models; Animals; Antigens; Autoimmune diseases; Autoimmune Diseases - immunology; Autoimmunity; B cells; Biology; Cancer; Cells, Cultured; Central nervous system; Central Nervous System - immunology; Chronic illnesses; Cytokines; Encephalomyelitis, Autoimmune, Experimental - immunology; Enzyme-Linked Immunosorbent Assay - methods; Experimental allergic encephalomyelitis; Flow Cytometry - methods; Gene Expression Regulation; Hazards; Health aspects; Helper cells; Immune system; Immunization; Immunology; Inflammation; Interferon; Interferon Type I - metabolism; Interferon-beta - metabolism; Interleukin 10; Interleukin 17; Interleukin-10 - metabolism; Interleukins - metabolism; Lymphocytes; Lymphocytes T; Medical research; Mice; Mice, Inbred C57BL; Mice, Knockout; Multiple sclerosis; Myelin; Nervous system; Nervous system diseases; Neurodegenerative diseases; Neurological diseases; Pathogenesis; Pathogens; Rodents; Signaling; Studies; T cells; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Th17 Cells - metabolism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0028432

Whereas the immune system is essential for host defense against pathogen infection or endogenous danger signals, dysregulated innate and adaptive immune cells may facilitate harmful inflammatory or autoimmune responses. In the CNS, chronic inflammation plays an important role in the pathogenesis of neurodegenerative diseases such as multiple sclerosis (MS). Our previous study has demonstrated a critical role for the type I IFN induction and signaling pathways in constraining Th17-mediated experimental autoimmune encephalomyelitis (EAE), an animal model of human MS. However, it remains unknown if self-reactive Th17 cells can be reprogrammed to have less encephalitogenic activities or even have regulatory effects through modulation of innate pathways. In this study, we investigated the direct effects of type I IFN on Th17 cells. Our data show that IFNβ treatment of T cells cultured under Th17 polarizing conditions resulted in reduced production of IL-17, but increased production of IL-10. We also found that IFNβ induced IL-10 production by antigen specific T cells derived from immunized mice. Furthermore, IFNβ treatment could suppress the encephalitogenic activity of myelin-specific T cells, and ameliorate clinical symptoms of EAE in an adoptive transfer model. Together, results from this study suggest that IFNβ may induce antigen-specific T cells to produce IL-10, which in turn negatively regulate Th17-mediate inflammatory and autoimmune response.