T helper 17 cells: discovery, function, and physiological trigger

In the few years since their discovery, T helper 17 cells (T(H)17) have been shown to play an important role in host defense against infections, and in tissue inflammation during autoimmunity. T(H)17 cells produce IL-17, IL-21, IL-10, and IL-22 cytokines, and thus have broad effects on a variety of tissues. Notably, the requirement for the immunosuppressive cytokine TGF-beta along with the pro-inflammatory cytokine IL-6 for T(H)17 differentiation supports the intimate relationship between the T(H)17 subset and FOXP3(+) regulatory T cells. Here, we discuss current knowledge on effector functions and differentiation of the T(H)17 lineage. Furthermore, we now know of a physiological stimulus for T(H)17 differentiation: innate immune recognition of cells undergoing apoptosis as a direct result of infection induces unique development of this subset. As our knowledge of T(H)17 and T regulatory cells grows, we are building on a new framework for the understanding of effector T cell differentiation and the biology of CD4(+) T cell adaptive immune responses.