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科学家绘制出溃疡性结肠炎中结肠CD8+T细胞的单细胞图谱
2020-08-05 16:04

英国牛津大学的Alison Simmons、Hashem Koohy等研究人员合作绘制出溃疡性结肠炎中结肠CD8+T细胞的单细胞图谱。相关论文于2020年8月3日在线发表于国际学术期刊《自然—医学》。

通过使用单细胞转录组学与T细胞受体库分析和质谱分析技术,研究人员绘制了健康和溃疡性结肠炎(UC)中人结肠CD8+T细胞图谱。研究人员揭示了CD8+T细胞组成中广泛的异质性,包括扩增的效应子和效应子后分化的CD8+T细胞。UC相关的CD8+效应T细胞可以触发组织破坏并产生肿瘤坏死因子(TNF)-α,而效应后细胞则具有先天的特征,可以采取调节功能来减轻过度的炎症反应。
 
因此,研究人员确定了健康和UC中的结肠CD8+T细胞表型,定义了它们的克隆关系,并表征了表达IL-26的终末分化功能障碍型UC CD8+T细胞,这些细胞能够减轻人源化IL-26转基因小鼠模型中的急性结肠炎。
 
据了解,结肠内抗原接触的淋巴细胞(如组织驻留记忆CD8+T细胞)可对重复的抗原暴露迅速做出反应。但是,它们的细胞表型以及驱动免疫调节和炎症的机制仍不清楚。
 
附:英文原文

Title: Single-cell atlas of colonic CD8 + T cells in ulcerative colitis

Author: Daniele Corridoni, Agne Antanaviciute, Tarun Gupta, David Fawkner-Corbett, Anna Aulicino, Marta Jagielowicz, Kaushal Parikh, Emmanouela Repapi, Steve Taylor, Dai Ishikawa, Ryo Hatano, Taketo Yamada, Wei Xin, Hubert Slawinski, Rory Bowden, Giorgio Napolitani, Oliver Brain, Chikao Morimoto, Hashem Koohy, Alison Simmons

Issue&Volume: 2020-08-03

Abstract: Colonic antigen-experienced lymphocytes such as tissue-resident memory CD8+ Tcells can respond rapidly to repeated antigen exposure. However, their cellular phenotypes and the mechanisms by which they drive immune regulation and inflammation remain unclear. Here we compiled an unbiased atlas of human colonic CD8+ Tcells in health and ulcerative colitis (UC) using single-cell transcriptomics with T-cell receptor repertoire analysis and mass cytometry. We reveal extensive heterogeneity in CD8+ T-cell composition, including expanded effector and post-effector terminally differentiated CD8+ Tcells. While UC-associated CD8+ effector Tcells can trigger tissue destruction and produce tumor necrosis factor (TNF)-α, post-effector cells acquire innate signatures to adopt regulatory functions that may mitigate excessive inflammation. Thus, we identify colonic CD8+ T-cell phenotypes in health and UC, define their clonal relationships and characterize terminally differentiated dysfunctional UC CD8+ Tcells expressing IL-26, which attenuate acute colitis in a humanized IL-26 transgenic mouse model.

DOI: 10.1038/s41591-020-1003-4

Source: https://www.nature.com/articles/s41591-020-1003-4

Nature Medicine:《自然—医学》,创刊于1995年。隶属于施普林格·自然出版集团,最新IF:87.241
官方网址:https://www.nature.com/nm/
投稿链接:https://mts-nmed.nature.com/cgi-bin/main.plex


本期文章:《自然—医学》:Online/在线发表

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