Vimentin modulates regulatory T cell receptor-ligand interactions at distal pole complex, leading to dysregulated host response to viral pneumonia

Autor: Ruihua Ma, Andrew D. Prigge, Tatiana P. Ortiz Serrano, Yuan Cheng, Jennifer M. Davis, Karen F. Lou, Walter A. Wood, Hanh Chi Do, Ziyou Ren, McKenzie M. Fulcer, Mary J. Lotesto, Benjamin D. Singer, Bria M. Coates, Karen M. Ridge
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Cell Reports, Vol 43, Iss 12, Pp 115056- (2024)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2024.115056
Popis: Summary: Forkhead box P3 (Foxp3)+ regulatory T cells (Tregs) resolve acute inflammation and repair the injured lung after viral pneumonia. Vimentin is a critical protein in the distal pole complex (DPC) of Tregs. This study reveals the inhibitory effect of vimentin on the suppressive and reparative capacity of Tregs. Treg-specific deletion of vimentin increases Helios+interleukin-18 receptor (IL-18R)+ Tregs, suppresses inflammatory immune cells, and enhances tissue repair, protecting Vimfl/flFoxp3YFP-cre mice from influenza-induced lung injury and mortality. Mechanistically, vimentin suppresses the induction of amphiregulin, an epidermal growth factor receptor (EGFR) ligand necessary for tissue repair, by sequestering IL-18R to the DPC and restricting receptor-ligand interactions. We propose that vimentin in the DPC of Tregs functions as a molecular switch, which could be targeted to regulate the immune response and enhance tissue repair in patients with severe viral pneumonia.
Databáze: Directory of Open Access Journals