# Acute exercise rewires the proteomic landscape of human immune cells

**Authors:** David Walzik, Niklas Joisten, Alan J. Metcalfe, Sebastian Proschinger, Alexander Schenk, Charlotte Wenzel, Alessa L. Henneberg, Martin Schneider, Silvia Calderazzo, Andreas Groll, Carsten Watzl, Christiane A. Opitz, Dominic Helm, Philipp Zimmer

PMC · DOI: 10.1038/s41467-025-68101-9 · 2026-01-02

## TL;DR

This study shows that high-intensity exercise causes bigger changes in immune cell proteins than moderate exercise, offering insights into how exercise intensity affects immune health.

## Contribution

The study reveals intensity-dependent proteomic changes in immune cells after exercise and identifies a signature linked to cardiorespiratory fitness.

## Key findings

- HIIE induces more pronounced proteomic changes in PBMCs compared to MICE.
- Exercise triggers alterations in immune cell activation and effector function pathways.
- An immunoproteomic signature predicts cardiorespiratory fitness and exercise-related health benefits.

## Abstract

The positive effect of exercise on the immune system is widely acknowledged, but the molecular response of immune cells to exercise remains largely unknown. Here, we perform mass-spectrometry-based proteomic analysis on peripheral blood mononuclear cells (PBMC) at a depth of >6000 proteins. Comparing high-intensity interval exercise (HIIE) and moderate-intensity continuous exercise (MICE), matched for time and workload, we identify versatile changes in the proteomic makeup of PBMCs and reveal profound alterations, related to effector function and immune cell activation pathways within one hour following exercise. These changes are more pronounced after HIIE compared to MICE and occur despite identical immune cell mobilization patterns between the two exercise conditions. We further identify an immunoproteomic signature that effectively predicts cardiorespiratory fitness, thus allowing insights into potential exercise-triggered adaptations and immunological health benefits that are mediated by exercise. This study provides a reliable data resource that expands our knowledge on how exercise modulates the immune system, and delivers biological evidence supporting the WHO 2020 guidelines, which highlight exercise intensity as a relevant factor to maintain health.

Exercise has considerable health benefit, including modulation of the immune system. Here the authors compare the molecular make-up of peripheral blood immune cells at resting state and upon a single bout of two different aerobic exercise modes by proteomics and show that although both exercise modes trigger similar changes, the effect is more pronounced after high intensity interval training.

## Linked entities

- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12775541/full.md

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Source: https://tomesphere.com/paper/PMC12775541