近日，美国斯隆凯特林研究所Alexander Y. Rudensky、Joris van der Veeken等研究人员合作揭示转录因子Foxp3依赖性和非依赖性的外周诱导Treg细胞功能。该研究于2022年6月13日在线发表于国际一流学术期刊《免疫》。

研究人员表示，表达转录因子Foxp3的调节性T（Treg）细胞是一种重要的双重来源的抑制性T细胞系。Foxp3在胸腺细胞和成熟的CD4⁺T细胞中的诱导，分别产生了胸腺（tTreg）和外周（pTreg）Treg细胞。当Treg细胞抑制自身免疫时，pTreg细胞则对食物和共生微生物群实施耐受。然而，Foxp3在pTreg细胞中的作用以及支持其分化的机制仍不甚明了。

研究人员使用遗传追踪来确定了微生物群诱导的pTreg细胞，并发现它们的许多区别特征与Foxp3无关。在没有Foxp3的情况下，结肠中持续存在谱系确立的、依赖微生物群的pTreg样细胞。虽然Foxp3对抑制Th17细胞程序、结肠炎和肥大症至关重要，但pTreg细胞以不依赖Foxp3的方式抑制了结肠效应T细胞的扩张。因此，Foxp3与耐受性信号独立地赋予pTreg功能的不同方面。

附：英文原文

Title: Genetic tracing reveals transcription factor Foxp3-dependent and Foxp3-independent functionality of peripherally induced Treg cells

Author: Joris van der Veeken, Clarissa Campbell, Yuri Pritykin, Michail Schizas, Jacob Verter, Wei Hu, Zhong-Min Wang, Fanny Matheis, Daniel Mucida, Louis-Marie Charbonnier, Talal A. Chatila, Alexander Y. Rudensky

Issue&Volume: 2022-06-13

Abstract: Regulatory T (Treg) cells expressing the transcription factor Foxp3 are an essentialsuppressive T cell lineage of dual origin: Foxp3 induction in thymocytes and matureCD4+ T cells gives rise to thymic (tTreg) and peripheral (pTreg) Treg cells, respectively.While tTreg cells suppress autoimmunity, pTreg cells enforce tolerance to food andcommensal microbiota. However, the role of Foxp3 in pTreg cells and the mechanismssupporting their differentiation remain poorly understood. Here, we used genetic tracingto identify microbiota-induced pTreg cells and found that many of their distinguishingfeatures were Foxp3 independent. Lineage-committed, microbiota-dependent pTreg-likecells persisted in the colon in the absence of Foxp3. While Foxp3 was critical forthe suppression of a Th17 cell program, colitis, and mastocytosis, pTreg cells suppressedcolonic effector T cell expansion in a Foxp3-independent manner. Thus, Foxp3 and thetolerogenic signals that precede and promote its expression independently confer distinctfacets of pTreg functionality.

DOI: 10.1016/j.immuni.2022.05.010

Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00230-8