2. Academic Validation
  3. TRIM11 attenuates Treg cell differentiation by p62-selective autophagic degradation of AIM2

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

  • Cell Rep. 2023 Oct 6;42(10):113231. doi: 10.1016/j.celrep.2023.113231.
Ting Yu 1,  Xiaofang Yang 2,  Qiang Fu 3,  Junyu Liang 4,  Xinger Wu 3,  Junli Sheng 5,  Yitian Chen 5,  Lu Xiao 2,  Yuxia Wu 6,  Dingnai Nie 5,  Xiaolong You 5,  Haiyan Mai 5,  Kang Chen 7,  Shengfeng Hu 8
Affiliations

Affiliations

  • 1 The Second Affiliated Hospital, The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Guangzhou Medical University, Guangzhou, China; Department of Pharmacy, Hainan General Hospital/Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China.
  • 2 Dermatology Hospital, Southern Medical University, Guangzhou, China.
  • 3 Department of Laboratory Medicine, Zhongshan City People's Hospital, Zhongshan, Guangdong, China.
  • 4 Department of Clinical Laboratory, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
  • 5 The Second Affiliated Hospital, The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Guangzhou Medical University, Guangzhou, China.
  • 6 Department of Pharmacy, Hainan General Hospital/Hainan Affiliated Hospital of Hainan Medical University, HaiKou, Hainan, China.
  • 7 Department of Laboratory Medicine, Zhongshan City People's Hospital, Zhongshan, Guangdong, China. Electronic address: ck521620@163.com.
  • 8 The Second Affiliated Hospital, The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Guangzhou Medical University, Guangzhou, China; Department of Rheumatology and Clinical Immunology, Zhujiang Hospital, Southern Medical University, Guangzhou, China. Electronic address: hushengfeng@gzhmu.edu.cn.
PMID: 37804507 DOI: 10.1016/j.celrep.2023.113231
Abstract

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.

Keywords

CP: Immunology; Treg cell differentiation; protein post-translational modification; selective autophagic degradation.

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