TRIM11 attenuates Treg cell differentiation by p62-selective autophagic degradation of AIM2

作者：Ting Yu, Xiaofan Yang, Qiang Fu, Junyu Liang, Xinger Wu, Junli Sheng, Yitian Chen, Xiao Lu, Yuxia Wu, Dingnai Nie, Xiaolong You, Haiyan Mai, Kang Chen, Shengfeng Hu · 发表于：Cell Reports · 年份：2023 · DOI：10.1016/j.celrep.2023.113231 · 被引用次数：15 · 研究领域：Immune Cell Function and Interaction、interferon and immune responses、Autophagy in Disease and Therapy

Ubiquitination is an important protein modification that regulates diverse biological processes, including CD4 + T cell differentiation and functions. However, the function of most E3 ubiquitin ligases in CD4 + T cell differentiation and CD4 + T cell-mediated pathological diseases remains unclear. In this study, we find that tripartite motif-containing motif 11 (TRIM11) specifically negatively regulates regulatory T (Treg) cell differentiation in CD4 + T cells and promotes autoimmune disease development in an AIM2-dependent manner. Mechanistically, TRIM11 interacts with absent in melanoma 2 (AIM2) and promotes the selective autophagic degradation of AIM2 by inducing AIM2 ubiquitination and binding to p62 in CD4 + T cells. AIM2 attenuates AKT and FOXO1 phosphorylation, MYC signaling, and glycolysis, thereby promoting the stability of Treg cells during experimental autoimmune encephalomyelitis (EAE). Our findings suggest that TRIM11 serves as a potential target for immunotherapeutic intervention for dysregulated immune responses that lead to autoimmunity and cancers.