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An immunoproteomic signature predicts cardiorespiratory fitness, supporting exercise intensity as a relevant health factor.",{"@graph":14,"@context":72},[15,34,55],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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[https://doi.org/10.1038/s41467-025-68101-9](https://doi.org/10.1038/s41467-025-68101-9)  \nAcute exercise rewires the proteomic landscape of human immune cells  \nReceived: 12 June 2025  \n\n| Accepted: 17 December 2025 |\n| --- |\n| |\n| Check for updates |\n\nDavid Walzik 1,9, Niklas Joisten 1,9, Alan J. Metcalfe2,3, Sebastian Proschinger1, Alexander Schenk1, Charlotte Wenzel1, Alessa L. Henneberg 4,  \nMartin Schneider5, Silvia Calderazzo6, Andreas Groll 7, Carsten Watzl 8, Christiane A. Opitz 4, Dominic Helm 5 & Philipp Zimmer 1   \nThe 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.  \nPhysical exercise is one of the most powerful strategies to prevent and counteract acute and chronic diseases across the entire human lifespan. The health beneﬁts of exercise are demonstrated by numerous clinical and observational trials1,2, but the underlying biological mechanisms are poorly understood. Given the broad implications of the immune system in protecting from disease, there is a clear rationale for comprehensive investigations of the impact of exercise on immune cells.  \nBoth the exercise-induced mobilization of speciﬁc immune cells into circulation as well as an increased cytokine release are welldescribed phenomena in exercise immunology3. However, few investigations have evaluated the molecular alterations in immune cells triggered by exercise. Bulk RNA sequencing revealed a complex interplay of up- and downregulated transcripts that peaked two minutes after exercise and returned to baseline within 30–60 min in  \n1Sports Medicine Research Group, Institute for Sport and Sport Science, TU Dortmund University, Dortmund, Germany. 2Department of Molecular and Cellular Sports Medicine, Institute of Cardiovascular Research and Sports Medicine, German Sport University Cologne, Cologne, Germany. 3Chest Unit, Centre for Human and Applied Physiological Sciences (CHAPS), Denmark Hill Campus, King’s College Hospital, King’s College London, London, United Kingdom. 4German Cancer Research Center (DKFZ), Heidelberg, Division of Metabolic Crosstalk in Cancer and the German Cancer Consortium (DKTK), DKFZ Core Center Heidelberg, Heidelberg, Germany. 5Proteomics Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany. 6Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany. 7Department of Statistics, TU Dortmund University, Dortmund, Germany. 8Leibniz Research Center for Working Environment and Human Factors at TU Dortmund (IfADo), Dortmund, Germany. 9These authors contributed equally: David Walzik, Niklas  \nJoisten. e-mail: [philipp.zimmer@tu-dortmund.de](philipp.zimmer@tu-dortmund.de)  \nperipheral blood mononuclear cells (PBMC). Enriched pathways were predominantly related to inﬂammatory signaling","cbCairZieD5prrb9","https://ap.wps.com/l/cbCairZieD5prrb9","pdf",4500872,16,"English","# Abstract\n## Proteomic response to HIIE and MICE\n## Effector function and immune activation pathways\n## Predicting cardiorespiratory fitness","[{\"question\":\"What is the main molecular focus of the study?\",\"answer\":\"The study investigates how acute exercise changes the proteomic landscape of human immune cells, specifically in PBMCs, using deep mass-spectrometry analysis.\"},{\"question\":\"How do HIIE and MICE differ in their proteomic effects?\",\"answer\":\"Proteomic alterations are more pronounced after high-intensity interval exercise (HIIE) than after moderate-intensity continuous exercise (MICE), even though immune cell mobilization patterns are matched and similar.\"},{\"question\":\"What practical use is suggested by the identified immunoproteomic signature?\",\"answer\":\"The study reports an immunoproteomic signature that effectively predicts cardiorespiratory fitness, offering insights into exercise-triggered adaptations and immunological health benefits.\"}]","Acute exercise rewires the proteomic landscape of human immune cells | PDF",1790743851]