Mechanism study of ubiquitination in T cell development and autoimmune disease

Front Immunol. 2024 Mar 18:15:1359933. doi: 10.3389/fimmu.2024.1359933. eCollection 2024.

Abstract

T cells play critical role in multiple immune processes including antigen response, tumor immunity, inflammation, self-tolerance maintenance and autoimmune diseases et. Fetal liver or bone marrow-derived thymus-seeding progenitors (TSPs) settle in thymus and undergo T cell-lineage commitment, proliferation, T cell receptor (TCR) rearrangement, and thymic selections driven by microenvironment composed of thymic epithelial cells (TEC), dendritic cells (DC), macrophage and B cells, thus generating T cells with diverse TCR repertoire immunocompetent but not self-reactive. Additionally, some self-reactive thymocytes give rise to Treg with the help of TEC and DC, serving for immune tolerance. The sequential proliferation, cell fate decision, and selection during T cell development and self-tolerance establishment are tightly regulated to ensure the proper immune response without autoimmune reaction. There are remarkable progresses in understanding of the regulatory mechanisms regarding ubiquitination in T cell development and the establishment of self-tolerance in the past few years, which holds great potential for further therapeutic interventions in immune-related diseases.

Keywords: E3 ubiquitin ligase; T cell development; TEC; Treg; autoimmune disease; self-tolerance; ubiquitination.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoimmune Diseases* / metabolism
  • Humans
  • Receptors, Antigen, T-Cell / metabolism
  • Thymocytes / metabolism
  • Thymus Gland
  • Ubiquitination

Substances

  • Receptors, Antigen, T-Cell

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (82303238, 31500077); Science and Technology Support Program of Sichuan Province (2024NSFSC3724, 20ZDYF0087 and 22ZDYF1357); Science and Technology Support Program of Chengdu (2021-YF05-02218-SN and 2022-YF05-01692-SN), Health Commission of Sichuan Province (20PJ212 and 21PJ146); The Third People’s Hospital of Chengdu Scientific Research Project (2023PI07, 2023PI09 and 2023PI18) and The Third People’s Hospital of Chengdu Clinical Research Program (CSY-YN-01-2023-013, CSY-YN-01-2023-019, CSY-YN-01-2023-020, CSY-YN-01-2023-021 and CSY-YN-01-2023-025).