Exercise reshapes cellular immunity toward anti-inflammation and diminishes CCR4 levels on LFA-1αhighCD4+ T cells in multiple sclerosis
- 1Sports Medicine Research Group, Institute for Sport and Sport Science, TU Dortmund University, Dortmund, Germany
Abstract
Multiple sclerosis (MS) represents a multifaceted neuroinflammatory disease for which regular exercise is now recommended by many healthcare institutions. Although preclinical studies indicate robust immunomodulatory effects of exercise, evidence from human studies is lacking. In this randomized controlled trial, persons with MS (pwMS) were assigned to three months of high-intensity interval training or a passive control condition, with outcomes assessed at baseline, after intervention, and a fourweek follow-up. Additionally, a healthy matched control group was included. Besides exercise-induced sustained increases in physical fitness, systemic inflammation was diminished and the Treg-to-TH17.1 ratio improved after exercise. Untargeted proteomic analysis of peripheral blood mononuclear cells covering >7000 proteins revealed an exercise-induced decrease in proteins implicated in inflammatory diseases (i.e., MTHFD2). This was supported by inferred transcription factor activity analysis, which indicated enhanced polarization of immune cells toward anti-inflammatory phenotypes at follow-up. Using flow cytometry, we identified an LFA-1highCD4+ T-cell subset that was associated with disease biomarkers and exhibited increased CCR4 expression compared to healthy matched subjects which was reduced after exercise. Our findings significantly expand knowledge of how exercise training exerts immediate and sustained immunomodulatory effects in pwMS and thereby strengthens the mechanistic rationale for exercise recommendations made by healthcare professionals.
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BibTeX
@misc{proschinger2026exercise,
title = {{Exercise reshapes cellular immunity toward anti-inflammation and diminishes CCR4 levels on LFA-1αhighCD4+ T cells in multiple sclerosis}},
author = {S. Proschinger and T. Wences Chirino and L. Hoenen and S. Trebing and N. Joisten and D. Walzik and N. Daube and G. Ellrichmann-Wilms and S. Ahmadi and M. Schneider and P. Zadora and D. L. Frey and S. G. Meuth and M. Pawlitzki and L. Masanneck and J. Kuhle and T. Ruck and R. Rehmann and A. L. Henneberg and C. A. Opitz and P. Zimmer},
howpublished = {medRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.05.26367365},
url = {https://www.medrxiv.org/content/10.64898/2026.11.05.26367365v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Exercise reshapes cellular immunity toward anti-inflammation and diminishes CCR4 levels on LFA-1αhighCD4+ T cells in multiple sclerosis
AU - S. Proschinger
AU - T. Wences Chirino
AU - L. Hoenen
AU - S. Trebing
AU - N. Joisten
AU - D. Walzik
AU - N. Daube
AU - G. Ellrichmann-Wilms
AU - S. Ahmadi
AU - M. Schneider
AU - P. Zadora
AU - D. L. Frey
AU - S. G. Meuth
AU - M. Pawlitzki
AU - L. Masanneck
AU - J. Kuhle
AU - T. Ruck
AU - R. Rehmann
AU - A. L. Henneberg
AU - C. A. Opitz
AU - P. Zimmer
PY - 2026
DA - 2026/11/05
PB - medRxiv
DO - 10.64898/2026.11.05.26367365
UR - https://www.medrxiv.org/content/10.64898/2026.11.05.26367365v1
AB - Multiple sclerosis (MS) represents a multifaceted neuroinflammatory disease for which regular exercise is now recommended by many healthcare institutions. Although preclinical studies indicate robust immunomodulatory effects of exercise, evidence from human studies is lacking. In this randomized controlled trial, persons with MS (pwMS) were assigned to three months of high-intensity interval training or a passive control condition, with outcomes assessed at baseline, after intervention, and a fourweek follow-up. Additionally, a healthy matched control group was included. Besides exercise-induced sustained increases in physical fitness, systemic inflammation was diminished and the Treg-to-TH17.1 ratio improved after exercise. Untargeted proteomic analysis of peripheral blood mononuclear cells covering >7000 proteins revealed an exercise-induced decrease in proteins implicated in inflammatory diseases (i.e., MTHFD2). This was supported by inferred transcription factor activity analysis, which indicated enhanced polarization of immune cells toward anti-inflammatory phenotypes at follow-up. Using flow cytometry, we identified an LFA-1highCD4+ T-cell subset that was associated with disease biomarkers and exhibited increased CCR4 expression compared to healthy matched subjects which was reduced after exercise. Our findings significantly expand knowledge of how exercise training exerts immediate and sustained immunomodulatory effects in pwMS and thereby strengthens the mechanistic rationale for exercise recommendations made by healthcare professionals.
ER -