Browsing Department of microbial immunoregulation (MIKI) by Authors
Microbiota-dependent expansion of testicular IL-17-producing Vγ6 γδ T cells upon puberty promotes local tissue immune surveillance.Wilharm, Anneke; Brigas, Helena C; Sandrock, Inga; Ribeiro, Miguel; Amado, Tiago; Reinhardt, Annika; Demera, Abdi; Hoenicke, Lisa; Strowig, Till; Carvalho, Tânia; et al. (Springer Nature, 2020-07-30)γδT 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 γδ (γδ17) 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 Vγ6-containing rearrangements. These γδ17 cells were the major source of IL-17 in the testis, whereas αβ T cells mostly provided interferon (IFN)-γ in situ. Importantly, testicular γδ17 cell homoeostasis was strongly dependent on the microbiota and Toll-like receptor (TLR4)/IL-1α/IL-23 signalling. We further found that γδ17 cells contributed to tissue surveillance in a model of experimental orchitis induced by intra-testicular inoculation of Listeria monocytogenes, as Tcrδ-/- and Il17-/- 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 γδ17 cell subset that infiltrates the testis at steady state, expands upon puberty and plays a crucial role in local tissue immune surveillance.