Zhang, L., Yuan, S., Cheng, G. & Guo, B. Type I IFN promotes IL-10 production from T cells to suppress Th17 cells and Th17-associated autoimmune inflammation. PLoS One 6, e28432

McMaster University, Canada
PLoS ONE (Impact Factor: 3.23). 12/2011; 6(12):e28432. DOI: 10.1371/journal.pone.0028432
Source: PubMed


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.

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Available from: Shunzong Yuan, Mar 21, 2015
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    • "It is likely that IFN-Is up-regulate PD-1 expression (e.g., on regulatory T cells) and PD-L1 (e.g., on DCs) on cells resulting in a milieu where PD-1/PD-L1 interactions occur; this could facilitate IL-10 production and exhaustion of T cell function during chronic viral infections (19, 76–80). A caveat here is that IFN-Is in some instances can also inhibit IL-10 production and IL-10 production can occur independently of IFN-I signaling (76, 81). Furthermore, IFN-Is up-regulate pro-apoptotic molecules such as Bak on T cells to induce apoptosis independently of T cell exhaustion (82). "
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    • "CD4 + T cells were collected from draining lymph nodes by positive selection, and the cytokines produced from MOG-reactive CD4 + T cells following restimulation with MOG 35–55 were examined. IFN-β treatment alone suppressed IFN-γ and IL-17 production (Fig. 1A and B), as described previously (Guo et al., 2008; Zhang et al., 2011). Sema4A alone did not change the production of IFN-γ and IL-17. "
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    • "es ( Rott et al . 1994 ; Tuohy et al . 2000 ) via reduction of Th17 phenotype ( Zhang et al . 2011 ) . Indeed , increased expression of IL - 10 accom - panies recovery from EAE / MS following established first line therapies ( group I interferons and glatiramer acetate ) and is in correlation with decreased levels of IL - 17 ( Stern et al . 2008 ; Zhang et al . 2011 ) . Along this line , CBD and THC were reported to increase IL - 10 secretion in murine T cell - mediated diabetes ( Weiss et al . 2006 ) and in activated splenocytes ( Newton et al . 1998 ) . The stronger CBD upregulation of IL - 10 expression over the effect observed with THC is in agreement with our recently published genome expressi"
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