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

作者：Yu, Ting; Yang, Xiaofang; Fu, Qiang; Liang, Junyu; Wu, Xinger; Sheng, Junli; Chen, Yitian; Xiao, Lu; Wu, Yuxia; Nie, Dingnai; You, Xiaolong; Mai, Haiyan; Chen, Kang^*; Hu, Shengfeng^*

来源：Cell Reports, 2023, 42(10): 113231.

DOI：10.1016/j.celrep.2023.113231

• REGULATORY T-CELLS
• PROMOTES PROLIFERATION
• INFLAMMASOME
• TUMORIGENICITY
• SUPPRESSES
• STABILITY
• MIGRATION
• UBIQUITIN
• INVASION
• IMMUNITY

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 dif-ferentiation and CD4+ T cell-mediated pathological diseases remains unclear. In this study, we find that tripar-tite 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. Mechanisti-cally, 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 experi-mental 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.

• 单位
  海南医学院; 广州医学院; 南方医科大学