Aging Induces an Nlrp3 Inflammasome-Dependent Expansion of Adipose B Cells That Impairs Metabolic Homeostasis
Christina D Camell, Patrick Günther, Aileen Lee, Emily L Goldberg, Olga Spadaro, Yun-Hee Youm, Andrzej Bartke, Gene B Hubbard, Yuji Ikeno, Nancy H Ruddle, Joachim Schultze, Vishwa Deep Dixit, Christina D Camell, Patrick Günther, Aileen Lee, Emily L Goldberg, Olga Spadaro, Yun-Hee Youm, Andrzej Bartke, Gene B Hubbard, Yuji Ikeno, Nancy H Ruddle, Joachim Schultze, Vishwa Deep Dixit
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.
Conflict of interest statement
Declaration of Interests
The authors declare no conflict of financial interest.
Copyright © 2019 Elsevier Inc. All rights reserved.
Figures
Source: PubMed