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Cognate recognition of microbial antigens defines constricted CD4+ T cell receptor repertoires in the inflamed colon
Immunity ( IF 25.5 ) Pub Date : 2021-09-27 , DOI: 10.1016/j.immuni.2021.08.014
Moritz Muschaweck 1 , Lydia Kopplin 2 , Fabio Ticconi 3 , Angela Schippers 4 , Aida Iljazovic 5 , Eric J C Gálvez 6 , Ali T Abdallah 7 , Norbert Wagner 4 , Ivan G Costa 8 , Till Strowig 6 , Oliver Pabst 2
Affiliation  

Key aspects of intestinal T cells, including their antigen specificity and their selection by the microbiota and other intestinal antigens, as well as the contribution of individual T cell clones to regulatory and effector functions, remain unresolved. Here we tracked adoptively transferred T cell populations to specify the interrelation of T cell receptor repertoire and the gut antigenic environment. We show that dominant TCRα clonotypes were shared between interferon-γ- and interleukin-17-producing but not regulatory Foxp3+ T cells. Identical TCRα clonotypes accumulated in the colon of different individuals, whereas antibiotics or defined colonization correlated with the expansion of distinct expanded T cell clonotypes. Our results demonstrate key aspects of intestinal CD4+ T cell activation and suggest that few microbial species exert a dominant effect on the intestinal T cell repertoire during colitis. We speculate that dominant proinflammatory T cell clones might provide a therapeutic target in human inflammatory bowel disease.



中文翻译:

微生物抗原的同源识别定义了发炎结肠中收缩的 CD4+ T 细胞受体库

肠道 T 细胞的关键方面,包括它们的抗原特异性和微生物群和其他肠道抗原的选择,以及单个 T 细胞克隆对调节和效应功能的贡献,仍未得到解决。在这里,我们跟踪过继转移的 T 细胞群,以指定 T 细胞受体库与肠道抗原环境的相互关系。我们表明主要的 TCRα 克隆型在产生干扰素-γ-和白细胞介素-17 的细胞之间共享,但不是调节性 Foxp3 + T 细胞。在不同个体的结肠中积累了相同的 TCRα 克隆型,而抗生素或确定的定植与不同扩增的 T 细胞克隆型的扩增相关。我们的结果证明了肠道 CD4 + 的关键方面T 细胞活化,并表明在结肠炎期间,很少有微生物物种对肠道 T 细胞库产生显着影响。我们推测显性促炎性 T 细胞克隆可能为人类炎症性肠病提供治疗靶点。

更新日期:2021-11-10
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