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

doi:10.1016/j.cmet.2019.10.006

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

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

111 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1024-1039.e6
Journal	Cell Metabolism
Volume	30
Issue number	6
DOIs	https://doi.org/10.1016/j.cmet.2019.10.006
State	Published - Dec 3 2019
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2019 Elsevier Inc.

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Aging Induces an Nlrp3 Inflammasome-Dependent Expansion of Adipose B Cells That Impairs Metabolic Homeostasis",

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.",

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

Abstract

Bibliographical note

Keywords

UN SDGs

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