Abstract

The primary function of Th17 cells appears to be the clearance of extracellular pathogens during infections. However, Th17 cells also promote inflammation and have been implicated in the pathogenesis of many experimental autoimmune diseases and human inflammatory conditions. Transforming growth factor β (TGFβ) is a critical differentiation factor for the generation of regulatory T (T-reg) cells, whereas the combination of interleukin 6 (IL6) and TGFβ induces the differentiation of pathogenic Th17 cells. Therefore, it is proposed that at the steady state (in the absence of any inflammatory stimuli), TGFβ, which is produced by various cells types including naturally occurring T-reg (nT-reg) cells, encourages the generation of induced T-reg (iT-reg) cells, which together with nT-reg cells keep autoreactive T cells under check. IL6, an acute phase protein produced by the activated immune system, inhibits the function of T-reg cells and instead promotes the differentiation of Th17 cells. Thus, IL6 plays a pivotal role in dictating the balance between the generation of T-reg and Th17 cells. This reciprocal relationship between T-reg and Th17 cells is further supported by the results obtained in IL6^−/− mice, which show a severe defect in the generation of Th17 cells and increased numbers of T-reg cells in the peripheral repertoire.