A transmissible γδ intraepithelial lymphocyte hyperproliferative phenotype is associated with the intestinal microbiota and confers protection against acute infection.

A transmissible γδ intraepithelial lymphocyte hyperproliferative phenotype is associated with the intestinal microbiota and confers protection against acute infection.
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DOI:
10.1038/s41385-022-00522-x
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发表时间:
2022-04
期刊:
影响因子:
8
通讯作者:
Edelblum, Karen L.
Edelblum, Karen L.
中科院分区:
医学1区
文献类型:
--
作者:
Jia, Luo;Wu, Guojun;Alonso, Sara;Zhao, Cuiping;Lemenze, Alexander;Lam, Yan Y.;Zhao, Liping;Edelblum, Karen L.

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表达Gamma Delta T细胞受体(Gamma Delta IEL)的上皮内淋巴细胞是抵御管腔微生物的第一道防线。尽管完整的微生物群的存在对于伽马三角洲IEL的发育是必不可少的,但几个微生物因素有助于维持这一哨兵种群。然而,在动态平衡条件下,特定的共生体是否影响伽马三角洲IEL室的种群还有待确定。我们发现了一种新的伽玛增量IEL高增殖表型,其特征是多个V伽马亚群的扩张。在抗生素治疗后,这种高增殖表型水平转移到表型正常的伽马三角洲IEL间隔室的小鼠被阻止,从而证明微生物区系对于观察到的伽马三角洲IEL的增加是必要的和充分的。此外,我们识别了两个由12个扩增序列变体(ASV)代表的小肠或粪便细菌公会,它们与伽马三角洲IEL扩展密切相关。使用活体显微镜,我们发现高度增殖的伽马三角洲IEL也显示出更多的迁移行为,从而增强了对细菌感染的保护。这些发现表明,转移一组特定的共生体可以调节伽马三角洲IEL的稳态和免疫监视,这可能提供一种新的手段来加强上皮屏障。
Intraepithelial lymphocytes expressing the gamma delta T cell receptor (gamma delta IELs) serve as a first line of defense against luminal microbes. Although the presence of an intact microbiota is dispensable for gamma delta IEL development, several microbial factors contribute to the maintenance of this sentinel population. However, whether specific commensals influence population of the gamma delta IEL compartment under homeostatic conditions has yet to be determined. We identified a novel gamma delta IEL hyperproliferative phenotype that is characterized by expansion of multiple Vgamma subsets. Horizontal transfer of this hyperproliferative phenotype to mice harboring a phenotypically normal gamma delta IEL compartment was prevented following antibiotic treatment, thus demonstrating that the microbiota is both necessary and sufficient for the observed increase in gamma delta IELs. Further, we identified two guilds of small intestinal or fecal bacteria represented by 12 amplicon sequence variants (ASV) that are strongly associated with gamma delta IEL expansion. Using intravital microscopy, we find that hyperproliferative gamma delta IELs also exhibit increased migratory behavior leading to enhanced protection against bacterial infection. These findings reveal that transfer of a specific group of commensals can regulate gamma delta IEL homeostasis and immune surveillance, which may provide a novel means to reinforce the epithelial barrier.
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