Eosinophils regulate adipose tissue inflammation and sustain physical and immunological fitness in old age

Daniel Brigger, Carsten Riether, Robin van Brummelen, Kira I. Mosher, Alicia Shiu, Zhaoqing Ding, Noemi Zbären, Pascal Gasser, Pascal Guntern, Hanadie Yousef, Joseph M. Castellano, Federico Storni, Neill Graff-Radford, Markus Britschgi, Denis Grandgirard, Magdalena Hinterbrandner, Mark Siegrist, Norman Moullan, Willy Hofstetter, Stephen L. LeibPeter M. Villiger, Johan Auwerx, Saul A. Villeda, Tony Wyss-Coray, Mario Noti, Alexander Eggel

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Adipose tissue eosinophils (ATEs) are important in the control of obesity-associated inflammation and metabolic disease. However, the way in which ageing impacts the regulatory role of ATEs remains unknown. Here, we show that ATEs undergo major age-related changes in distribution and function associated with impaired adipose tissue homeostasis and systemic low-grade inflammation in both humans and mice. We find that exposure to a young systemic environment partially restores ATE distribution in aged parabionts and reduces adipose tissue inflammation. Approaches to restore ATE distribution using adoptive transfer of eosinophils from young mice into aged recipients proved sufficient to dampen age-related local and systemic low-grade inflammation. Importantly, restoration of a youthful systemic milieu by means of eosinophil transfers resulted in systemic rejuvenation of the aged host, manifesting in improved physical and immune fitness that was partially mediated by eosinophil-derived IL-4. Together, these findings support a critical function of adipose tissue as a source of pro-ageing factors and uncover a new role of eosinophils in promoting healthy ageing by sustaining adipose tissue homeostasis.

Original languageEnglish (US)
Pages (from-to)688-702
Number of pages15
JournalNature Metabolism
Volume2
Issue number8
DOIs
StatePublished - Aug 1 2020

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology (medical)
  • Internal Medicine
  • Cell Biology

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    Brigger, D., Riether, C., van Brummelen, R., Mosher, K. I., Shiu, A., Ding, Z., Zbären, N., Gasser, P., Guntern, P., Yousef, H., Castellano, J. M., Storni, F., Graff-Radford, N., Britschgi, M., Grandgirard, D., Hinterbrandner, M., Siegrist, M., Moullan, N., Hofstetter, W., ... Eggel, A. (2020). Eosinophils regulate adipose tissue inflammation and sustain physical and immunological fitness in old age. Nature Metabolism, 2(8), 688-702. https://doi.org/10.1038/s42255-020-0228-3