Interleukin-17-Producing γδ T Cells Selectively Expand in Response to Pathogen Products and Environmental Signals

Summaryγδ T cells are an innate source of interleukin-17 (IL-17), preceding the development of the adaptive T helper 17 (Th17) cell response. Here we show that IL-17-producing T cell receptor γδ (TCRγδ) T cells share characteristic features with Th17 cells, such as expression of chemokine receptor 6 (CCR6), retinoid orphan receptor (RORγt), aryl hydrocarbon receptor (AhR), and IL-23 receptor. AhR expression in γδ T cells was essential for the production of IL-22 but not for optimal IL-17 production. In contrast to Th17 cells, CCR6+IL-17-producing γδ T cells, but not other γδ T cells, express Toll-like receptors TLR1 and TLR2, as well as dectin-1, but not TLR4 and could directly interact with certain pathogens. This process was amplified by IL-23 and resulted in expansion, increased IL-17 production, and recruitment of neutrophils. Thus, innate receptor expression linked with IL-17 production characterizes TCRγδ T cells as an efficient first line of defense that can orchestrate an inflammatory response to pathogen-derived as well as environmental signals long before Th17 cells have sensed bacterial invasion