美国波士顿儿童医院Talal A. Chatila研究组发现，调节性T细胞来源的TGF-β1调控过敏和自身免疫。这一研究成果于2020年10月20日在线发表在国际学术期刊《免疫》上。

研究人员发现，由于白介素4（IL-4）和STAT6依赖性的Tgfb1转录抑制，食物过敏（FA）中调节性T（Treg）细胞表达的转化生长因子β1（TGF-β1）会减少。这些变化是通过Treg细胞特异性Tgfb1单等位基因失活来塑造的，该失活通过削弱微生物群依赖的视黄酸受体相关的孤儿γ（ROR-γt）⁺Treg细胞分化而诱导过敏性调节异常。通过用梭状芽胞杆菌属物种治疗可以挽救这种失调，该物种可以上调Treg细胞中Tgfb1的表达。双等位基因缺乏导致致命的自身免疫，产生大量自身抗体，以及T滤泡辅助细胞和B细胞反应失调。

这些结果确定了Treg细胞来源的TGF-β1在不同检查点中以Tgfb1基因剂量和微生物群依赖性方式来调节变态反应和自身免疫的作用。

据悉，Treg细胞差异性调控过敏和自身免疫反应的机制仍不清楚。

附：英文原文

Title: Regulatory T Cell-Derived TGF-β1 Controls Multiple Checkpoints Governing Allergy and Autoimmunity

Author: Jacob A. Turner, Emmanuel Stephen-Victor, Sen Wang, Magali Noval Rivas, Azza Abdel-Gadir, Hani Harb, Ye Cui, Manoussa Fanny, Louis-Marie Charbonnier, Jason Jun Hung Fong, Mehdi Benamar, Leighanne Wang, Oliver T. Burton, Kushagra Bansal, Lynn Bry, Chengsong Zhu, Quan-Zhen Li, Rachel L. Clement, Hans C. Oettgen, Elena Crestani, Rima Rachid, Peter T. Sage, Talal A. Chatila

Issue&Volume: 2020-10-20

Abstract: The mechanisms by which regulatory T (Treg) cells differentially control allergicand autoimmune responses remain unclear. We show that Treg cells in food allergy (FA)had decreased expression of transforming growth factor beta 1 (TGF-β1) because ofinterleukin-4 (IL-4)- and signal transducer and activator of transciription-6 (STAT6)-dependentinhibition of Tgfb1 transcription. These changes were modeled by Treg cell-specific Tgfb1 monoallelic inactivation, which induced allergic dysregulation by impairing microbiota-dependentretinoic acid receptor-related orphan receptor gamma t (ROR-γt)+ Treg cell differentiation. This dysregulation was rescued by treatment with Clostridialesspecies, which upregulated Tgfb1 expression in Treg cells. Biallelic deficiency precipitated fatal autoimmunity withintense autoantibody production and dysregulated T follicular helper and B cell responses.These results identify a privileged role of Treg cell-derived TGF-β1 in regulatingallergy and autoimmunity at distinct checkpoints in a Tgfb1 gene dose- and microbiota-dependent manner.

DOI: 10.1016/j.immuni.2020.10.002

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30414-3