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Cell Metab. 2019 Dec 3;30(6):1024-1039.e6. doi: 10.1016/j.cmet.2019.10.006. Epub 2019 Nov 14.

Aging Induces an Nlrp3 Inflammasome-Dependent Expansion of Adipose B Cells That Impairs Metabolic Homeostasis.

Author information

1
Department of Comparative Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
2
Genomics and Immunoregulation, LIMES-Institute, University of Bonn, 53115 Bonn, Germany; PRECISE Platform for Single Cell Genomics and Epigenomics at the University of Bonn and the German Center for Neurodegenerative Diseases, Bonn, Germany.
3
Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62702, USA.
4
Department of Pathology, Barshop Institute, UT Health San Antonio, San Antonio, TX 78229, USA.
5
Department of Pathology, Barshop Institute, UT Health San Antonio, San Antonio, TX 78229, USA; Geriatric Research Education and Clinical Center, Audie L. Murphy VA Hospital, South Texas Veterans Health Care System, San Antonio, TX 78229, USA.
6
Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT 06520, USA.
7
Department of Comparative Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA; Yale Center for Research on Aging, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address: vishwa.dixit@yale.edu.

Abstract

During aging, visceral adiposity is often associated with alterations in adipose tissue (AT) leukocytes, inflammation, and metabolic dysfunction. However, the contribution of AT B cells in immunometabolism during aging is unexplored. Here, we show that aging is associated with an expansion of a unique population of resident non-senescent aged adipose B cells (AABs) found in fat-associated lymphoid clusters (FALCs). AABs are transcriptionally distinct from splenic age-associated B cells (ABCs) and show greater expansion in female mice. Functionally, whole-body B cell depletion restores proper lipolysis and core body temperature maintenance during cold stress. Mechanistically, the age-induced FALC formation, AAB, and splenic ABC expansion is dependent on the Nlrp3 inflammasome. Furthermore, AABs express IL-1R, and inhibition of IL-1 signaling reduces their proliferation and increases lipolysis in aging. These data reveal that inhibiting Nlrp3-dependent B cell accumulation can be targeted to reverse metabolic impairment in aging AT.

KEYWORDS:

B cell depletion; IL-1 signaling; Nlrp3 inflammasome; adipose tissue B cells; age-associated B cells; aging; fat-associated lymphoid cluster; growth hormone receptor; inflammaging; lipolysis

PMID:
31735593
DOI:
10.1016/j.cmet.2019.10.006

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