Microbiota-dependent expansion of testicular IL-17-producing Vγ6+γδ T cells upon puberty promotes local tissue immune surveillance

gamma delta T cells represent the majority of lymphocytes in several mucosal tissues where they contribute to tissue homoeostasis, microbial defence and wound repair. Here we characterise a population of interleukin (IL) 17-producing gamma delta (gamma delta 17) T cells that seed the testis of naive C57BL/6 mice, expand at puberty and persist throughout adulthood. We show that this population is foetal-derived and displays a T-cell receptor (TCR) repertoire highly biased towards V gamma 6-containing rearrangements. These gamma delta 17 cells were the major source of IL-17 in the testis, whereas alpha beta T cells mostly provided interferon (IFN)-gamma in situ. Importantly, testicular gamma delta 17 cell homoeostasis was strongly dependent on the microbiota and Toll-like receptor (TLR4)/IL-1 alpha/IL-23 signalling. We further found that gamma delta 17 cells contributed to tissue surveillance in a model of experimental orchitis induced by intra-testicular inoculation ofListeria monocytogenes, asTcr delta(-/-)andIl17(-/-)infected mice displayed higher bacterial loads than wild-type (WT) controls and died 3 days after infection. Altogether, this study identified a previously unappreciated foetal-derived gamma delta 17 cell subset that infiltrates the testis at steady state, expands upon puberty and plays a crucial role in local tissue immune surveillance.

Automated summary

This study identified a previously underappreciated fetal-derived subset of γδ17 cells that infiltrate the testis at steady state, expand upon puberty, and play a crucial role in local tissue immune surveillance.