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

Autor:	Ma R; Division of Pulmonary and Critical Care, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. Electronic address: ruihua.ma@northwestern.edu., Prigge AD; Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA., Ortiz Serrano TP; Division of Pulmonary and Critical Care, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA., Cheng Y; Division of Pulmonary and Critical Care, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA., Davis JM; Division of Pulmonary and Critical Care, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA., Lou KF; Division of Pulmonary and Critical Care, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA., Wood WA; Division of Pulmonary and Critical Care, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA., Do HC; Division of Pulmonary and Critical Care, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA., Ren Z; Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA., Fulcer MM; Division of Pulmonary and Critical Care, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA., Lotesto MJ; Division of Pulmonary and Critical Care, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA., Singer BD; Division of Pulmonary and Critical Care, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA., Coates BM; Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA., Ridge KM; Division of Pulmonary and Critical Care, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Department of Cell and Developmental Biology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. Electronic address: kridge@northwestern.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2024 Dec 07; Vol. 43 (12), pp. 115056. Date of Electronic Publication: 2024 Dec 07.
DOI:	10.1016/j.celrep.2024.115056
Abstrakt:	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 Vim fl/fl Foxp3 YFP-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. Competing Interests: Declaration of interests B.D.S. holds United States patent no. US 10,905,706 B2, “Compositions and Methods to Accelerate Resolution of Acute Lung Inflammation,” and serves on the scientific advisory board of Zoe Biosciences. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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