Human intestinal tissue-resident memory T cells comprise transcriptionally and functionally distinct subsets.
Human intestinal tissue-resident memory T cells comprise transcriptionally and functionally distinct subsets.
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DOI：
10.1016/j.celrep.2020.108661
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发表时间：
2021-01-19
期刊：
影响因子：
8.8
通讯作者：
Allan PJ
中科院分区：
文献类型：
--
作者：
FitzPatrick MEB;Provine NM;Garner LC;Powell K;Amini A;Irwin SL;Ferry H;Ambrose T;Friend P;Vrakas G;Reddy S;Soilleux E;Klenerman P;Allan PJ
组织驻留记忆 T (TRM) 细胞在感染、癌症和自身免疫中提供关键的适应性免疫反应。然而，人类肠道 TRM 细胞的转录异质性仍不清楚。在这里，我们通过研究来自肠道移植受者的供体来源的 TRM 细胞来研究人类 TRM 细胞的转录和功能异质性。单细胞转录谱鉴定了 CD8+ TRM 细胞的两种转录状态，由 ITGAE 和 ITGB2 表达来描述。我们定义了区分这些群体的转录特征，包括细胞毒性和居住相关基因的差异表达。对浸润移植物的受体衍生细胞和来自健康肠道的淋巴细胞进行流式细胞术，证实了这些 CD8+ TRM 表型。 CD8+ CD69+CD103+ TRM 细胞产生白细胞介素-2 (IL-2)，并表现出更强的多功能细胞因子产量，而 β2-整合素+CD69+CD103− TRM 细胞具有更高的颗粒酶表达。对肠道 CD4+ T 细胞的分析发现了几个相似之处，包括 β2-整合素+ 群体。这些结果共同描述了人肠道 CD4+ 和 CD8+ TRM 细胞的转录、表型和功能异质性。人类肠道移植物用于鉴定真正的 TRM 细胞 单细胞 RNA 测序鉴定出两个不同的 CD8+ TRM 子集 CD103+CD69+ 和 CD103−CD69+ TRM 细胞子集显示出不同的定位和功能 β2-整合素在 CD103− TRM 细胞上高度表达 历史上很难准确鉴定人类组织驻留记忆 T (TRM) 细胞。菲茨帕特里克等人。使用人类肠道移植模型更明确地识别人类 TRM 细胞。单细胞 RNA 测序揭示了肠道 CD8+ TRM 细胞的两个转录上不同的群体，它们在定位和功能上表现出差异。
Tissue-resident memory T (TRM) cells provide key adaptive immune responses in infection, cancer, and autoimmunity. However, transcriptional heterogeneity of human intestinal TRM cells remains undefined. Here, we investigate transcriptional and functional heterogeneity of human TRM cells through study of donor-derived TRM cells from intestinal transplant recipients. Single-cell transcriptional profiling identifies two transcriptional states of CD8+ TRM cells, delineated by ITGAE and ITGB2 expression. We define a transcriptional signature discriminating these populations, including differential expression of cytotoxicity- and residency-associated genes. Flow cytometry of recipient-derived cells infiltrating the graft, and lymphocytes from healthy gut, confirm these CD8+ TRM phenotypes. CD8+ CD69+CD103+ TRM cells produce interleukin-2 (IL-2) and demonstrate greater polyfunctional cytokine production, whereas β2-integrin+CD69+CD103− TRM cells have higher granzyme expression. Analysis of intestinal CD4+ T cells identifies several parallels, including a β2-integrin+ population. Together, these results describe the transcriptional, phenotypic, and functional heterogeneity of human intestinal CD4+ and CD8+ TRM cells. Human intestinal transplants were used to identify bona fide TRM cells Single-cell RNA sequencing identifies two distinct CD8+ TRM subsets CD103+CD69+ and CD103−CD69+ TRM cell subsets show distinct localization and function β2-integrin is highly expressed on CD103− TRM cells It has been historically difficult to accurately identify human tissue-resident memory T (TRM) cells. FitzPatrick et al. use a model of human intestinal transplantation to more definitively identify human TRM cells. Single-cell RNA sequencing reveals two transcriptionally distinct populations of intestinal CD8+ TRM cells, which show differences in localization and function.
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影响因子：
8
作者：
Fergusson JR;Hühn MH;Swadling L;Walker LJ;Kurioka A;Llibre A;Bertoletti A;Holländer G;Newell EW;Davis MM;Sverremark-Ekström E;Powrie F;Capone S;Folgori A;Barnes E;Willberg CB;Ussher JE;Klenerman P
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Jahnsen, Frode L.
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