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Microbiota-dependent expansion of testicular IL-17-producing Vγ6+ γδ T cells upon puberty promotes local tissue immune surveillance.
Mucosal Immunology ( IF 7.9 ) Pub Date : 2020-07-30 , DOI: 10.1038/s41385-020-0330-6
Anneke Wilharm 1 , Helena C Brigas 2 , Inga Sandrock 1 , Miguel Ribeiro 2 , Tiago Amado 2 , Annika Reinhardt 1 , Abdi Demera 1 , Lisa Hoenicke 3 , Till Strowig 3 , Tânia Carvalho 2 , Immo Prinz 1 , Julie C Ribot 2
Affiliation  

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.



中文翻译:

青春期时睾丸产生 IL-17 的 Vγ6+ γδ T 细胞的微生物依赖性扩增可促进局部组织免疫监视。

γδT 细胞代表多种粘膜组织中的大多数淋巴细胞,它们有助于组织稳态、微生物防御和伤口修复。在这里,我们描述了一群产生白细胞介素 (IL) 17 的 γδ (γδ17) T 细胞,这些细胞在幼稚 C57BL/6 小鼠的睾丸中播种,在青春期扩张并持续整个成年期。我们发现这个群体是胎儿来源的,并表现出高度偏向于含有 Vγ6 重排的 T 细胞受体 (TCR) 库。这些 γδ17 细胞是睾丸中 IL-17 的主要来源,而 αβ T 细胞主要在原位提供干扰素 (IFN)-γ。重要的是,睾丸 γδ17 细胞稳态强烈依赖于微生物群和 Toll 样受体 (TLR4)/IL-1α/IL-23 信号传导。我们进一步发现,在睾丸内接种单核细胞增生李斯特菌诱导的实验性睾丸炎模型中,γδ17 细胞有助于组织监测,因为Tcrδ - /−Il17 -/−感染的小鼠比野生型 (WT) 对照小鼠表现出更高的细菌载量感染后3天死亡。总而言之,这项研究发现了一种先前未被认识的胎儿来源的 γδ17 细胞亚群,该亚群在稳定状态下浸润睾丸,在青春期扩展并在局部组织免疫监视中发挥至关重要的作用。

更新日期:2020-07-30
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