Interleukin-17-producing γδ T (γδ17) cells in inflammatory diseases

Interleukin-17 (IL-17) is a pro-inflammatory cytokine and is involved in the development of many diseases. Recent studies have revealed that IL-17-producing gamma delta T cells (gamma delta 17 cells) in addition to IL-17-producing CD4(+) T cells [T helper type 17 (Th17) cells] are often the main producers of IL-17 in mouse models of inflammatory diseases. gamma delta T cells are functionally committed during intra-thymic differentiation. gamma delta thymocytes capable of producing IL-17, which express the transcription factor retinoic-acid-receptor-related orphan receptor gamma t and the signature cytokine receptor IL-23R, leave the thymus, and produce IL-17 rapidly by the stimulation with IL-1 beta and IL-23 in the periphery. Therefore, gamma delta 17 cells play important roles in the early phase of host defence against pathogens and in inflammatory diseases. gamma delta T cells that can produce IL-17 are also increased in the skin of patients with psoriasis and in peripheral blood of patients with ankylosing sclerosis. Indeed, the therapy targeting IL-17 has been approved or is in clinical trials, and proved to be very efficient to treat psoriasis, psoriatic arthritis and ankylosing sclerosis. In this review, we discuss recent knowledge about the pathophysiological function of gamma delta 17 cells in infection and inflammatory diseases and therapeutic advances targeting IL-17.