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

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

doi:10.1016/j.celrep.2024.115056

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

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

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/flFoxp3^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.

Original language	English (US)
Article number	115056
Journal	Cell reports
Volume	43
Issue number	12
DOIs	https://doi.org/10.1016/j.celrep.2024.115056
State	Published - Dec 24 2024

Funding

We thank the Robert H. Lurie Comprehensive Cancer Center of Northwestern University for the use of the Flow Cytometry Core Facility. Histology services were provided by the Northwestern University Mouse Histology and Phenotyping Laboratory. Bright-field imaging was performed at the Northwestern University Center for Advanced Microscopy. Confocal microscopic imaging was kindly supported by Robert Goldman and Vladimir I. Gelfand, Department of Cell and Developmental Biology, Northwestern University. R.M. was supported by a David and Christina Cugell Fellowship ; A.D.P. was supported by the Gorter Family Foundation , NIH NHLBI 5T32HL076139-18 , the ATS Research Program , and the Parker B. Francis Fellowship Program ; T.P.O.S. was supported by NIH 5T32HL076139 ; B.D.S. was supported by NIH R01HL149883 , R01HL153122 , P01HL154998 , P01AG049665 , U19AI135964 , and U19AI181102 ; B.M.C. was supported by the American Lung Association and NIH R01HL168672 and P01HL154998 ; and K.M.R. was supported by NIH P01 HL154998 , R01HL166807 , and P01AG049665 .

Keywords

AREG
CP: Immunology
IL-18R
Tregs
distal pole complex
epidermal growth factor receptor
lung injury
lung repair
regulatory T cells
vimentin
viral pneumonia

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.celrep.2024.115056

Cite this

Ma, R., Prigge, A. D., Ortiz Serrano, T. P., Cheng, Y., Davis, J. M., Lou, K. F., Wood, W. A., Do, H. C., Ren, Z., Fulcer, M. M., Lotesto, M. J., Singer, B. D., Coates, B. M., & Ridge, K. M. (2024). Vimentin modulates regulatory T cell receptor-ligand interactions at distal pole complex, leading to dysregulated host response to viral pneumonia. Cell reports, 43(12), Article 115056. https://doi.org/10.1016/j.celrep.2024.115056

@article{023b6f23a8184a77807d3602a344df4d,

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

abstract = "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.",

keywords = "AREG, CP: Immunology, IL-18R, Tregs, distal pole complex, epidermal growth factor receptor, lung injury, lung repair, regulatory T cells, vimentin, viral pneumonia",

author = "Ruihua Ma and Prigge, {Andrew D.} and {Ortiz Serrano}, {Tatiana P.} and Yuan Cheng and Davis, {Jennifer M.} and Lou, {Karen F.} and Wood, {Walter A.} and Do, {Hanh Chi} and Ziyou Ren and Fulcer, {McKenzie M.} and Lotesto, {Mary J.} and Singer, {Benjamin D.} and Coates, {Bria M.} and Ridge, {Karen M.}",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s)",

year = "2024",

month = dec,

day = "24",

doi = "10.1016/j.celrep.2024.115056",

language = "English (US)",

volume = "43",

journal = "Cell reports",

issn = "2639-1856",

publisher = "Cell Press",

number = "12",

}

Ma, R , Prigge, AD, Ortiz Serrano, TP, Cheng, Y, Davis, JM, Lou, KF, Wood, WA, Do, HC, Ren, Z, Fulcer, MM, Lotesto, MJ, Singer, BD , Coates, BM & Ridge, KM 2024, 'Vimentin modulates regulatory T cell receptor-ligand interactions at distal pole complex, leading to dysregulated host response to viral pneumonia', Cell reports, vol. 43, no. 12, 115056. https://doi.org/10.1016/j.celrep.2024.115056

TY - JOUR

T1 - Vimentin modulates regulatory T cell receptor-ligand interactions at distal pole complex, leading to dysregulated host response to viral pneumonia

AU - Ma, Ruihua

AU - Prigge, Andrew D.

AU - Ortiz Serrano, Tatiana P.

AU - Cheng, Yuan

AU - Davis, Jennifer M.

AU - Lou, Karen F.

AU - Wood, Walter A.

AU - Do, Hanh Chi

AU - Ren, Ziyou

AU - Fulcer, McKenzie M.

AU - Lotesto, Mary J.

AU - Singer, Benjamin D.

AU - Coates, Bria M.

AU - Ridge, Karen M.

PY - 2024/12/24

Y1 - 2024/12/24

N2 - 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.

AB - 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.

KW - AREG

KW - CP: Immunology

KW - IL-18R

KW - Tregs

KW - distal pole complex

KW - epidermal growth factor receptor

KW - lung injury

KW - lung repair

KW - regulatory T cells

KW - vimentin

KW - viral pneumonia

UR - http://www.scopus.com/inward/record.url?scp=85211132593&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85211132593&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2024.115056

DO - 10.1016/j.celrep.2024.115056

M3 - Article

C2 - 39645657

AN - SCOPUS:85211132593

SN - 2639-1856

VL - 43

JO - Cell reports

JF - Cell reports

IS - 12

M1 - 115056

ER -

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this