Suppression of autoimmune inflammation of the central nervous system by interleukin 10 secreted by interleukin 27-stimulated T cells

Excessive inflammation occurs during infection and autoimmunity in mice lacking the alpha- subunit of the interleukin 27 (IL-27) receptor. The molecular mechanisms underlying this increased inflammation are incompletely understood. Here we report that IL-27 upregulated IL-10 in effector T cells that produced interferon-gamma and expressed the transcription factor T- bet but did not express the transcription factor Foxp3. These IFN-gamma(+) T- bet(+) Foxp3(-) cells resembled effector T cells that have been identified as the main source of host-protective IL- 10 during inflammation. IL-27-induced production of IL- 10 was associated with less secretion of IL- 17, and exogenous IL- 27 reduced the severity of adoptively transferred experimental autoimmune encephalomyelitis by a mechanism dependent on IL-10. Our data show that IL-27-induced production of IL- 10 by effector T cells contributes to the immunomodulatory function of IL-27.