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Ubc13 maintains the suppressive function of regulatory T cells and prevents their conversion into effector-like T cells

机译:Ubc13维持调节性T细胞的抑制功能并阻止其转化为效应子样T细胞

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摘要

The maintenance of immune homeostasis requires regulatory T cells (T reg cells). Here we found that T reg cell-specific ablation of Ubc13, a Lys63 (K63)-specific ubiquitin-conjugating enzyme, caused aberrant T cell activation and autoimmunity. Although Ubc13 deficiency did not affect the survival of T reg cells or expression of the transcription factor Foxp3, it impaired the in vivo suppressive function of T reg cells and rendered them sensitive to the acquisition of T helper type 1 (T H1) cell- and interleukin 17 (IL-17)-producing helper T (T H17) cell-like effector phenotypes. This function of Ubc13 involved its downstream target, the kinase IKK. The Ubc13-IKK signaling axis controlled the expression of specific T reg cell effector molecules, including IL-10 and SOCS1. Collectively, our findings suggest that the Ubc13-IKK signaling axis regulates the molecular program that maintains T reg cell function and prevents T reg cells from acquiring inflammatory phenotypes.
机译:维持免疫稳态需要调节性T细胞(T reg细胞)。在这里,我们发现Ubc13(一种Lys63(K63)特异性泛素结合酶)的T reg细胞特异性消融引起异常的T细胞活化和自身免疫。尽管Ubc13缺乏症不会影响T reg细胞的存活或转录因子Foxp3的表达,但它削弱了T reg细胞的体内抑制功能,并使它们对获得1型T辅助细胞(T H1)敏感。产生白介素17(IL-17)的辅助T(T H17)细胞样效应子表型。 Ubc13的功能涉及其下游靶标激酶IKK。 Ubc13-IKK信号轴控制着特定T reg细胞效应分子(包括IL-10和SOCS1)的表达。总的来说,我们的研究结果表明,Ubc13-IKK信号轴调节维持T reg细胞功能并防止T reg细胞获得炎症表型的分子程序。

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