Peptidase inhibitor 16 promotes inflammatory arthritis by suppressing Foxp3 expression via regulating K48-linked ubiquitin degradation Bmi-1 in regulatory T cells

Peptidase inhibitor 16 promotes inflammatory arthritis by suppressing Foxp3 expression via regulating K48-linked ubiquitin degradation Bmi-1 in regulatory T cells

Copyright © 2023. Published by Elsevier Inc.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 259(2024) vom: 01. Feb., Seite 109883
1. Verfasser: Wang, Fang (VerfasserIn)
Weitere Verfasser: Gu, Xin, Lin, Shiyu, Wu, Qin, Sun, Yuankai, Zhang, Qian, Luo, Aishu, Feng, Xiaoke, Wang, Lei, Xu, Lingxiao, Sun, Wei, Tan, Wenfeng
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2024
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Bmi-1 Foxp3 PI16 Regulatory T cells Rheumatoid arthritis Forkhead Transcription Factors Foxp3 protein, mouse Protease Inhibitors mehr... Ubiquitin PI16 protein, human protease inhibitor 16, mouse FOXP3 protein, human Bmi1 protein, mouse BMI1 protein, human
Beschreibung
Zusammenfassung:Copyright © 2023. Published by Elsevier Inc.
Abnormalities of regulatory T cells (Tregs) has been suggested in rheumatoid arthritis (RA), and Forkhead box P3 (Foxp3) is the key transcriptional factor of Tregs expression. However, the underlying molecular mechanism remains unclear. Here, we demonstrated peptidase inhibitor 16 (PI16) was significantly increased in the peripheral blood, synovial fluid, and synovial tissue from RA patients. PI16 transgenic mice (PI16Tg) aggravated arthritis severity partly through suppressing Foxp3 expression. Mechanistically, PI16 could interact with and stabilize Bmi-1 in Tregs via inhibiting K48-linked polyubiquitin of Bmi-1, which promotes the enrichment of repressive histone mark in Foxp3 promoter. Furthermore, Bmi-1 specific inhibitor PTC209 could restore Foxp3 expression and alleviate arthritis progression in PI16Tg mice, accompanied by increased recruitment of active histone mark in the promoter of Tregs. Our results suggest that PI16-Bmi-1 axis plays an important role in RA and other autoimmune diseases by suppressing Foxp3 expression in Tregs via Bmi-1-mediated histone modification
Beschreibung:Date Completed 01.02.2024
Date Revised 10.04.2024
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2023.109883