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. Leib; Peter M. Villiger; Johan Auwerx; Saul A. Villeda; Tony Wyss-Coray; Mario Noti; Alexander Eggel

doi:10.1038/s42255-020-0228-3

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

Neurology

Research output: Contribution to journal › Article › peer-review

13 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 language	English (US)
Pages (from-to)	688-702
Number of pages	15
Journal	Nature Metabolism
Volume	2
Issue number	8
DOIs	https://doi.org/10.1038/s42255-020-0228-3
State	Published - Aug 1 2020

ASJC Scopus subject areas

Physiology (medical)
Internal Medicine
Endocrinology, Diabetes and Metabolism
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

Brigger, D, Riether, C, van Brummelen, R, Mosher, KI, Shiu, A, Ding, Z, Zbären, N, Gasser, P, Guntern, P, Yousef, H, Castellano, JM, Storni, F, Graff-Radford, N, Britschgi, M, Grandgirard, D, Hinterbrandner, M, Siegrist, M, Moullan, N, Hofstetter, W, Leib, SL, Villiger, PM, Auwerx, J, Villeda, SA, Wyss-Coray, T, Noti, M & Eggel, A 2020, 'Eosinophils regulate adipose tissue inflammation and sustain physical and immunological fitness in old age', Nature Metabolism, vol. 2, no. 8, pp. 688-702. https://doi.org/10.1038/s42255-020-0228-3

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title = "Eosinophils regulate adipose tissue inflammation and sustain physical and immunological fitness in old age",

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.",

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

note = "Funding Information: We thank past and present members of the Noti, Eggel and Wyss-Coray laboratories for discussions and valuable input; A.-L. Huguenin, U. L{\"u}thi and C. Kr{\"u}ger for technical support; J. J. Lee and H.-U. Simon for providing IL-5 transgenic mice; M. Fux, A. Odermatt and the DBMR FACSlab for technical support with cell sorting; the staff and animal caretakers of the Central Animal Facility in Bern for their advice and support; K. Rufibach for valuable discussions; and H. Maeker and the Stanford Human Immune Monitoring Center for their help with qPCR multiplex array. J.A. is supported by grants from {\'E}cole Polytechnique F{\'e}d{\'e}rale de Lausanne, the Swiss National Science Foundation (no. 31003A-140780), the AgingX programme of the Swiss Initiative for Systems Biology (no. 51RTP0-151019) and the NIH (no. R01AG043930). This work was funded by the National Institute on Aging (no. R01AG053382 to S.A.V. and nos. AG045034 and DP1AG053015 to T.W.-C.), the Department of Veterans Affairs (to T.W.-C.), the Glenn Center for the Biology of Aging (to T.W.-C.), a Novartis grant for Medical-Biological Research (no. 15B100 to M.N.), a FreeNovation Novartis grant (to M.N) and by grants from the Fondation Acteria (to A.E. and M.N.) and Velux Stiftung (no. 1095 to A.E.). Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2020",

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doi = "10.1038/s42255-020-0228-3",

language = "English (US)",

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T1 - Eosinophils regulate adipose tissue inflammation and sustain physical and immunological fitness in old age

AU - Brigger, Daniel

AU - Riether, Carsten

AU - van Brummelen, Robin

AU - Mosher, Kira I.

AU - Shiu, Alicia

AU - Ding, Zhaoqing

AU - Zbären, Noemi

AU - Gasser, Pascal

AU - Guntern, Pascal

AU - Yousef, Hanadie

AU - Castellano, Joseph M.

AU - Storni, Federico

AU - Graff-Radford, Neill

AU - Britschgi, Markus

AU - Grandgirard, Denis

AU - Hinterbrandner, Magdalena

AU - Siegrist, Mark

AU - Moullan, Norman

AU - Hofstetter, Willy

AU - Leib, Stephen L.

AU - Villiger, Peter M.

AU - Auwerx, Johan

AU - Villeda, Saul A.

AU - Wyss-Coray, Tony

AU - Noti, Mario

AU - Eggel, Alexander

N1 - Funding Information: We thank past and present members of the Noti, Eggel and Wyss-Coray laboratories for discussions and valuable input; A.-L. Huguenin, U. Lüthi and C. Krüger for technical support; J. J. Lee and H.-U. Simon for providing IL-5 transgenic mice; M. Fux, A. Odermatt and the DBMR FACSlab for technical support with cell sorting; the staff and animal caretakers of the Central Animal Facility in Bern for their advice and support; K. Rufibach for valuable discussions; and H. Maeker and the Stanford Human Immune Monitoring Center for their help with qPCR multiplex array. J.A. is supported by grants from École Polytechnique Fédérale de Lausanne, the Swiss National Science Foundation (no. 31003A-140780), the AgingX programme of the Swiss Initiative for Systems Biology (no. 51RTP0-151019) and the NIH (no. R01AG043930). This work was funded by the National Institute on Aging (no. R01AG053382 to S.A.V. and nos. AG045034 and DP1AG053015 to T.W.-C.), the Department of Veterans Affairs (to T.W.-C.), the Glenn Center for the Biology of Aging (to T.W.-C.), a Novartis grant for Medical-Biological Research (no. 15B100 to M.N.), a FreeNovation Novartis grant (to M.N) and by grants from the Fondation Acteria (to A.E. and M.N.) and Velux Stiftung (no. 1095 to A.E.). Publisher Copyright: © 2020, The Author(s), under exclusive licence to Springer Nature Limited.

PY - 2020/8/1

Y1 - 2020/8/1

N2 - 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.

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

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