Regulation of Protective and Pathogenic Th17 Responses

The recent description of a T helper lymphocyte subset (Th17) that is characterized by the production of IL-17, TNF-α , IL-6, IL-22, and GM-CSF has substantially influenced current concepts of the pathogenesis of inflammatory diseases such as arthritis or encephalitis. Contrasting with the prevailing dogma that held IFN-γ producing Th1 cells responsible for the pathogenesis of most organ-specific autoimmune diseases it had been noted for some time that IFN-γ-/- mice were more susceptible to arthritis and encephalitis than their wild-type, littermates and that IL-12 was dispensable for disease induction. Recently it has become clear, that Th17 cells are of central importance for the pathogenesis of inflammatory diseases. The differentiation of naive Th cells into Th17 is triggered by antigen recognition in the presence of both IL-6 and TGF-β . IL-23, a heterodimeric cytokine which shares the p40 chain with IL-12 is an important survival factor for Th17 whereas IL-27, another member of the IL-12 family strongly inhibits Th17 production. Here we review the protective and pathogenic functions of Th17 in host defense and inflammatory diseases.