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ILC3选择微生物特异性调节性T细胞在肠道建立耐受性
2022-09-11 21:35

近日,美国康奈尔大学Gregory F. Sonnenberg及其研究团队发现,ILC3选择微生物特异性调节性T细胞在肠道建立耐受性。相关论文于2022年9月7日在线发表于国际学术期刊《自然》。

研究人员定义了一个关键的途径,其控制对微生物群作出反应并表达转录因子RORγt的炎症性与耐受性T细胞的命运。研究人员以单细胞分辨率对小鼠肠道引流淋巴结的所有RORγt+免疫细胞进行了分析,发现T调节(Treg)细胞和淋巴组织诱导者样第3组先天性淋巴细胞(ILC3)的主导性存在,它们在滤泡间区域共同定位。这些ILC3有别于胸腺外AIRE表达细胞,大量表达主要组织相容性复合体II类,是促进微生物特异性ROγt+Treg细胞并防止其扩展为炎症性T辅助17细胞的必要和充分条件。这是通过ILC3介导的抗原呈递、αV整合素和对白细胞介素-2的竞争发生的。

最后,单细胞分析表明,ILC3和RORγt+Treg细胞之间的相互作用在炎症性肠病中受到损害。这些结果定义了一个范式,即ILC3选择抗原特异性RORγt+Treg细胞,并反对T辅助17细胞,从而建立对微生物群和肠道健康的免疫耐受。

据悉,哺乳动物肠道的微生物定植引起了炎症性或耐受性T细胞反应,但控制这些不同结果的机制仍然知之甚少,越来越多的证据表明,肠道微生物群的异常免疫与感染性、炎症性和恶性疾病有因果关系。

附:英文原文

Title: ILC3s select microbiota-specific regulatory T cells to establish tolerance in the gut

Author: Lyu, Mengze, Suzuki, Hiroaki, Kang, Lan, Gaspal, Fabrina, Zhou, Wenqing, Goc, Jeremy, Zhou, Lei, Zhou, Jordan, Zhang, Wen, Shen, Zeli, Fox, James G., Sockolow, Robbyn E., Laufer, Terri M., Fan, Yong, Eberl, Gerard, Withers, David R., Sonnenberg, Gregory F.

Issue&Volume: 2022-09-07

Abstract: Microbial colonization of the mammalian intestine elicits inflammatory or tolerogenic T cell responses, but the mechanisms controlling these distinct outcomes remain poorly understood, and accumulating evidence indicates that aberrant immunity to intestinal microbiota is causally associated with infectious, inflammatory and malignant diseases1,2,3,4,5,6,7,8. Here we define a critical pathway controlling the fate of inflammatory versus tolerogenic T cells that respond to the microbiota and express the transcription factor RORγt. We profiled all RORγt+ immune cells at single-cell resolution from the intestine-draining lymph nodes of mice and reveal a dominant presence of T regulatory (Treg) cells and lymphoid tissue inducer-like group 3 innate lymphoid cells (ILC3s), which co-localize at interfollicular regions. These ILC3s are distinct from extrathymic AIRE-expressing cells, abundantly express major histocompatibility complex class II, and are necessary and sufficient to promote microbiota-specific RORγt+ Treg cells and prevent their expansion as inflammatory T helper 17 cells. This occurs through ILC3-mediated antigen presentation, αV integrin and competition for interleukin-2. Finally, single-cell analyses suggest that interactions between ILC3s and RORγt+ Treg cells are impaired in inflammatory bowel disease. Our results define a paradigm whereby ILC3s select for antigen-specific RORγt+ Treg cells, and against T helper 17 cells, to establish immune tolerance to the microbiota and intestinal health.

DOI: 10.1038/s41586-022-05141-x

Source: https://www.nature.com/articles/s41586-022-05141-x

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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