小柯机器人

美国哈佛医学院Vijay K. Kuchroo、Aviv Regev等研究人员合作发现，干细胞样肠道Th17细胞在自身免疫过程中产生致病性效应T细胞。相关论文于2021年12月6日在线发表在《细胞》杂志上。

研究人员通过结合命运图谱和超过84,000个Th17细胞的转录组和TCR克隆型的剖析，在体内描述了在平衡状态和中枢神经系统自身免疫性炎症期间组织Th17细胞的异质性、可塑性和迁移表型。器官间和器官内的单细胞分析显示，一个稳定的、类似干细胞的TCF1⁺ IL-17⁺ SLAMF6⁺群体被输送到肠道，在那里它被微生物群维持，为IL-23驱动的致脑性GM^-CSF⁺ IFN-γ⁺ CXCR6⁺ T细胞的产生提供了一个现成的细胞库。这项研究确定了IL-17⁺非致病性和GM-CSF⁺及IFN-γ⁺致病性Th17群体之间的直接体内关系，并提供了一种机制，通过这种机制，肠道Th17细胞可指导肠外自身免疫性疾病。

据介绍，虽然肠道Th17细胞对维持组织平衡至关重要，但最近的研究表明它们在肠道外自身免疫性疾病（包括多发性硬化症）的发展中发挥了作用。然而，组织Th17细胞介导这些对立功能的机制仍然是未知的。

附：英文原文

Title: Stem-like intestinal Th17 cells give rise to pathogenic effector T cells during autoimmunity

Author: Alexandra Schnell, Linglin Huang, Meromit Singer, Anvita Singaraju, Rocky M. Barilla, Brianna M.L. Regan, Alina Bollhagen, Pratiksha I. Thakore, Danielle Dionne, Toni M. Delorey, Mathias Pawlak, Gerd Meyer zu Horste, Orit Rozenblatt-Rosen, Rafael A. Irizarry, Aviv Regev, Vijay K. Kuchroo

Issue&Volume: 2021-12-06

Abstract: While intestinal Th17 cells are critical for maintaining tissue homeostasis, recentstudies have implicated their roles in the development of extra-intestinal autoimmunediseases including multiple sclerosis. However, the mechanisms by which tissue Th17cells mediate these dichotomous functions remain unknown. Here, we characterized theheterogeneity, plasticity, and migratory phenotypes of tissue Th17 cells in vivo by combined fate mapping with profiling of the transcriptomes and TCR clonotypesof over 84,000 Th17 cells at homeostasis and during CNS autoimmune inflammation. Inter-and intra-organ single-cell analyses revealed a homeostatic, stem-like TCF1+ IL-17+ SLAMF6+ population that traffics to the intestine where it is maintained by the microbiota,providing a ready reservoir for the IL-23-driven generation of encephalitogenic GM-CSF+ IFN-γ+ CXCR6+ T cells. Our study defines a direct in vivo relationship between IL-17+ non-pathogenic and GM-CSF+ and IFN-γ+ pathogenic Th17 populations and provides a mechanism by which homeostatic intestinalTh17 cells direct extra-intestinal autoimmune disease.

DOI: 10.1016/j.cell.2021.11.018

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)01333-7