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

被引：83

作者：

Brigger, Daniel ^{[1
,2
]}

Riether, Carsten ^{[3
,4
]}

van Brummelen, Robin ^{[1
,2
]}

Mosher, Kira, I ^{[5
,13
]}

Shiu, Alicia ^{[5
,14
]}

Ding, Zhaoqing ^{[5
,15
]}

Zbaren, Noemi ^{[1
,2
]}

Gasser, Pascal ^{[1
,2
]}

Guntern, Pascal ^{[1
,2
]}

Yousef, Hanadie ^{[5
]}

Castellano, Joseph M. ^{[6
]}

Storni, Federico ^{[1
,2
,16
]}

Graff-Radford, Neill ^{[7
]}

Britschgi, Markus ^{[5
,17
]}

Grandgirard, Denis ^{[8
]}

Hinterbrandner, Magdalena ^{[3
,4
]}

Siegrist, Mark ^{[2
]}

Moullan, Norman ^{[9
]}

Hofstetter, Willy ^{[2
]}

Leib, Stephen L. ^{[8
]}

Villiger, Peter M. ^{[1
,2
]}

Auwerx, Johan ^{[9
]}

Villeda, Saul A. ^{[10
]}

Wyss-Coray, Tony ^{[5
,11
]}

Noti, Mario ^{[12
,18
]}

Eggel, Alexander ^{[1
,2
]}

机构：

[1] Univ Bern, Bern Univ Hosp, Dept Rheumatol Immunol & Allergol, Bern, Switzerland

[2] Univ Bern, Dept BioMed Res, Bern, Switzerland

[3] Univ Bern, Dept BioMed Res, Tumor Immunol, Bern, Switzerland

[4] Univ Bern, Bern Univ Hosp, Dept Med Oncol, Inselspital, Bern, Switzerland

[5] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA USA

[6] Icahn Sch Med Mt Sinai, Nash Family Dept Neurosci, Dept Neurol, Friedman Brain Inst,Ronald M Loeb Ctr Alzheimers, New York, NY 10029 USA

[7] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA

[8] Univ Bern, Inst Infect Dis, Bern, Switzerland

[9] Ecole Polytech Fed Lausanne, Lab Integrat & Syst Physiol, Lausanne, Switzerland

[10] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA

[11] Stanford Univ, Wu Tsai Neurosci Inst, Stanford, CA 94305 USA

[12] Univ Bern, Inst Pathol, Div Expt Pathol, Bern, Switzerland

[13] Univ Calif Berkeley, Dept Chem & Biol Engn, Berkeley, CA 94720 USA

[14] Amplitude Analyt Inc, San Francisco, CA USA

[15] Johnson & Johnson Pharmaceut Res & Dev LLC, San Diego, CA USA

[16] Univ Bern, Bern Univ Hosp, Dept Visceral Surg & Med, Bern, Switzerland

[17] F Hoffmann La Roche Ltd, Roche Innovat Ctr Basel, Neurosci Discovery, Roche Pharma Res & Early Dev, Basel, Switzerland

[18] Nestle Res, Dept Gastrointestinal Hlth, Immunol, Lausanne, Switzerland

来源：

NATURE METABOLISM | 2020年 / 2卷 / 08期

基金：

瑞士国家科学基金会;

关键词：

CALORIC RESTRICTION; T-CELLS; INSULIN-RESISTANCE; STEM-CELLS; LIFE-SPAN; REJUVENATION; MACROPHAGES; PERSPECTIVES; EXPRESSION; INCREASE;

D O I：

10.1038/s42255-020-0228-3

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：688 / +

页数：30

共 66 条

[1] Aging, Clonality, and Rejuvenation of Hematopoietic Stem Cells [J].

Akunuru, Shailaja ;

Geiger, Hartmut .

TRENDS IN MOLECULAR MEDICINE, 2016, 22 (08) :701-712

[2] Exposure to a youthful circulaton rejuvenates bone repair through modulation of β-catenin [J].

Baht, Gurpreet S. ;

Silkstone, David ;

Vi, Linda ;

Nadesan, Puviindran ;

Amani, Yasha ;

Whetstone, Heather ;

Wei, Qingxia ;

Alman, Benjamin A. .

NATURE COMMUNICATIONS, 2015, 6

[3] Caloric restriction reverses hepatic insulin resistance in aging rats by decreasing visceral fat [J].

Barzilai, N ;

Banerjee, S ;

Hawkins, M ;

Chen, W ;

Rossetti, L .

JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (07) :1353-1361

[4] Caloric Restriction Delays Disease Onset and Mortality in Rhesus Monkeys [J].

Colman, Ricki J. ;

Anderson, Rozalyn M. ;

Johnson, Sterling C. ;

Kastman, Erik K. ;

Kosmatka, Kristopher J. ;

Beasley, T. Mark ;

Allison, David B. ;

Cruzen, Christina ;

Simmons, Heather A. ;

Kemnitz, Joseph W. ;

Weindruch, Richard .

SCIENCE, 2009, 325 (5937) :201-204

[5] Rejuvenation of aged progenitor cells by exposure to a young systemic environment [J].

Conboy, IM ;

Conboy, MJ ;

Wagers, AJ ;

Girma, ER ;

Weissman, IL ;

Rando, TA .

NATURE, 2005, 433 (7027) :760-764

[6] Notch-mediated restoration of regenerative potential to aged muscle [J].

Conboy, IM ;

Conboy, MJ ;

Smythe, GM ;

Rando, TA .

SCIENCE, 2003, 302 (5650) :1575-1577

[7] Dynamic changes in mouse hematopoietic stem cell numbers during aging [J].

de Haan, G ;

Van Zant, G .

BLOOD, 1999, 93 (10) :3294-3301

[8] Open source clustering software [J].

de Hoon, MJL ;

Imoto, S ;

Nolan, J ;

Miyano, S .

BIOINFORMATICS, 2004, 20 (09) :1453-1454

[9] Functionally competent eosinophils differentiated ex vivo in high purity from normal mouse bone marrow [J].

Dyer, Kimberly D. ;

Moser, Jennifer M. ;

Czapiga, Meggan ;

Siegel, Steven J. ;

Percopo, Caroline M. ;

Rosenberg, Helene F. .

JOURNAL OF IMMUNOLOGY, 2008, 181 (06) :4004-4009

[10] A revival of parabiosis in biomedical research [J].

Eggel, Alexander ;

Wyss-Coray, Tony .

SWISS MEDICAL WEEKLY, 2014, 144

← 1 2 3 4 5 6 7 →