Exercise reduces inflammatory cell production and cardiovascular inflammation via instruction of hematopoietic progenitor cells

Vanessa Frodermann, David Rohde, Gabriel Courties, Nicolas Severe, Maximilian J. Schloss, Hajera Amatullah, Cameron S. McAlpine, Sebastian Cremer, Friedrich F. Hoyer, Fei Ji, Ian D. van Koeverden, Fanny Herisson, Lisa Honold, Gustavo Santos Masson, Shuang Zhang, Jana Grune, Yoshiko Iwamoto, Stephen P. Schmidt, Gregory R. Wojtkiewicz, I. Hsiu LeeKarin Gustafsson, Gerard Pasterkamp, Saskia C.A. de Jager, Ruslan I. Sadreyev, Jean MacFadyen, Peter Libby, Paul Ridker, David T. Scadden, Kamila Naxerova, Kate L. Jeffrey, Filip K. Swirski, Matthias Nahrendorf

Research output: Contribution to journalArticlepeer-review

108 Scopus citations

Abstract

A sedentary lifestyle, chronic inflammation and leukocytosis increase atherosclerosis; however, it remains unclear whether regular physical activity influences leukocyte production. Here we show that voluntary running decreases hematopoietic activity in mice. Exercise protects mice and humans with atherosclerosis from chronic leukocytosis but does not compromise emergency hematopoiesis in mice. Mechanistically, exercise diminishes leptin production in adipose tissue, augmenting quiescence-promoting hematopoietic niche factors in leptin-receptor-positive stromal bone marrow cells. Induced deletion of the leptin receptor in Prrx1-creERT2; Leprfl/fl mice reveals that leptin’s effect on bone marrow niche cells regulates hematopoietic stem and progenitor cell (HSPC) proliferation and leukocyte production, as well as cardiovascular inflammation and outcomes. Whereas running wheel withdrawal quickly reverses leptin levels, the impact of exercise on leukocyte production and on the HSPC epigenome and transcriptome persists for several weeks. Together, these data show that physical activity alters HSPCs via modulation of their niche, reducing hematopoietic output of inflammatory leukocytes.

Original languageEnglish
Pages (from-to)1761-1771
Number of pages11
JournalNature Medicine
Volume25
Issue number11
DOIs
StatePublished - 1 Nov 2019
Externally publishedYes

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