当前位置: X-MOL 学术Immunity › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Regulatory T Cell-Derived TGF-β1 Controls Multiple Checkpoints Governing Allergy and Autoimmunity
Immunity ( IF 25.5 ) Pub Date : 2020-10-20 , DOI: 10.1016/j.immuni.2020.10.002
Jacob A Turner 1 , Emmanuel Stephen-Victor 1 , Sen Wang 1 , Magali Noval Rivas 2 , Azza Abdel-Gadir 1 , Hani Harb 1 , Ye Cui 1 , Manoussa Fanny 1 , Louis-Marie Charbonnier 1 , Jason Jun Hung Fong 1 , Mehdi Benamar 1 , Leighanne Wang 1 , Oliver T Burton 3 , Kushagra Bansal 4 , Lynn Bry 5 , Chengsong Zhu 6 , Quan-Zhen Li 6 , Rachel L Clement 7 , Hans C Oettgen 1 , Elena Crestani 1 , Rima Rachid 1 , Peter T Sage 7 , Talal A Chatila 1
Affiliation  

The mechanisms by which regulatory T (Treg) cells differentially control allergic and 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 of interleukin-4 (IL-4)- and signal transducer and activator of transciription-6 (STAT6)-dependent inhibition of Tgfb1 transcription. These changes were modeled by Treg cell-specific Tgfb1 monoallelic inactivation, which induced allergic dysregulation by impairing microbiota-dependent retinoic acid receptor-related orphan receptor gamma t (ROR-γt)+ Treg cell differentiation. This dysregulation was rescued by treatment with Clostridiales species, which upregulated Tgfb1 expression in Treg cells. Biallelic deficiency precipitated fatal autoimmunity with intense autoantibody production and dysregulated T follicular helper and B cell responses. These results identify a privileged role of Treg cell-derived TGF-β1 in regulating allergy and autoimmunity at distinct checkpoints in a Tgfb1 gene dose- and microbiota-dependent manner.



中文翻译:

调节性 T 细胞衍生的 TGF-β1 控制控制过敏和自身免疫的多个检查点

调节性 T (Treg) 细胞差异控制过敏和自身免疫反应的机制仍不清楚。我们发现食物过敏 (FA) 中的 Treg 细胞由于白细胞介素 4 (IL-4) 和信号转导和转录激活因子 6 (STAT6) 依赖性而降低了转化生长因子 β1 (TGF-β1) 的表达Tgfb1转录的抑制。这些变化是通过 Treg 细胞特异性Tgfb1单等位基因失活来模拟的,失活通过损害微生物群依赖性视黄酸受体相关的孤儿受体 γt (ROR-γt) + Treg 细胞分化来诱导过敏性失调。这种失调通过梭状芽胞杆菌属物种的治疗得以挽救,它上调了 Tgfb1Treg 细胞中的表达。双等位基因缺乏会导致致命的自身免疫,产生强烈的自身抗体和失调的 T 滤泡辅助细胞和 B 细胞反应。这些结果确定了 Treg 细胞衍生的 TGF-β1 在以Tgfb1基因剂量和微生物群依赖性方式在不同检查点调节过敏和自身免疫方面的特殊作用。

更新日期:2020-12-15
down
wechat
bug