肠道微生物诱导产生CD4+ T细胞表型

作者：杨超月

本期文章：《自然—免疫学》：Online/在线发表

美国哈佛医学院Christophe Benoist及Diane Mathis研究组合作发现，肠道CD4+ T细胞表型是由微生物塑造的连续体而非TH决定。该研究于2021年1月18日发表于国际学术期刊《自然-免疫学》。

为了确定体内效应淋巴细胞（Teff）在组织中所处的真实状态，研究人员将单细胞转录组和染色质分析应用于无菌或普通小鼠或经一系列表型偏向微生物诱导小鼠的结肠Teff细胞。研究人员发现干扰素（IFN）或髓样特异性转录物标记了Teff子集，但是转录组或染色质结构无法解析常规辅助性T细胞（TH）子集的离散簇。

在基线或感染的不同时间段，通常用于标记TH的细胞因子或蛋白质转录本分布在极化的连续体中，并进行了功能验证。由单个祖细胞克隆形成了产生IFN-γ和白介素（IL）-17的细胞。大部分转录差异与感染因子相关而与产生的细胞因子无关，染色质变异主要反映了激活蛋白（AP）-1和IFN调节因子（IRF）转录因子（TF）家族的活性，而不是典型主要调节因子T-bet、GATA3或RORγ子集。

据悉，一般通过CD4+ Teff产生的细胞因子将其分类。

附：英文原文

Title: Gut CD4 + T cell phenotypes are a continuum molded by microbes, not by T H archetypes

Author: Evgeny Kiner, Elijah Willie, Brinda Vijaykumar, Kaitavjeet Chowdhary, Hugo Schmutz, Jodie Chandler, Alexandra Schnell, Pratiksha I. Thakore, Graham LeGros, Sara Mostafavi, Diane Mathis, Christophe Benoist

Issue&Volume: 2021-01-18

Abstract: CD4+ effector lymphocytes (Teff) are traditionally classified by the cytokines they produce. To determine the states that Teff cells actually adopt in frontline tissues in vivo, we applied single-cell transcriptome and chromatin analyses to colonic Teff cells in germ-free or conventional mice or in mice after challenge with a range of phenotypically biasing microbes. Unexpected subsets were marked by the expression of the interferon (IFN) signature or myeloid-specific transcripts, but transcriptome or chromatin structure could not resolve discrete clusters fitting classic helper T cell (TH) subsets. At baseline or at different times of infection, transcripts encoding cytokines or proteins commonly used as TH markers were distributed in a polarized continuum, which was functionally validated. Clones derived from single progenitors gave rise to both IFN-γ- and interleukin (IL)-17-producing cells. Most of the transcriptional variance was tied to the infecting agent, independent of the cytokines produced, and chromatin variance primarily reflected activities of activator protein (AP)-1 and IFN-regulatory factor (IRF) transcription factor (TF) families, not the canonical subset master regulators T-bet, GATA3 or RORγ.

DOI: 10.1038/s41590-020-00836-7

Source: https://www.nature.com/articles/s41590-020-00836-7

期刊信息

Nature Immunology：《自然—免疫学》，创刊于2000年。隶属于施普林格·自然出版集团，最新IF：23.53
官方网址：https://www.nature.com/ni/
投稿链接：https://mts-ni.nature.com/cgi-bin/main.plex