Interferon-alpha controls IL-17 expression in vitro and in vivo

The type I interferons interferon alpha (IFN alpha) and IFN beta are the first line of defense potently induced upon viral infection, and at the same time are immunomodulatory cytokines bridging innate and adaptive immunity. T cells secreting interleukin-17 (IL-17) have recently been identified to regulate neutrophil-mediated inflammation, and have been implicated in the pathogenesis of experimental colitis and human inflammatory bowel disease, and are considered to regulate the inflammatory response in these models. We therefore hypothesized that type I IFNs as sentinels of viral infection might counteract the development of Th17 cells. We studied the effects of IFN alpha on IL-17 mRNA and protein expression in human peripheral blood mononuclear cells (PBMC) and during differentiation of human and murine naive T cells into Th17 cells. In patients with ulcerative colitis (UC) treated systemically with IFN alpha, we studied colonic expression of IL-17 before and 4 weeks after therapy. IFNa potently suppressed IL-17 production in PBMC both at the mRNA and protein level. Th17 differentiation of human and murine naive T cells was markedly suppressed in the presence of IFN alpha. UC patients exhibited increased IL-17 expression in colonic tissue biopsies compared to healthy controls, which was down-regulated during IFN alpha therapy. IL-17 expression in colonic tissue correlated with clinical remission in these patients. Our data suggest that IFN alpha down-regulates IL-17 expression and Th17 differentiation in vitro and in vivo. As a corollary, these effects might play a role in the mode of action of type I IFNs in the treatment of various diseases. (C) 2008 Elsevier GmbH. All rights reserved.