Aging induces Nlrp3 inflammasome dependent adipose B cell expansion to impair metabolic homeostasis

Camell, C. D.; Lee, A.; Günther, P.; Goldberg, E. L.; Spadaro, O.; Youm, Y.-H.; Bartke, A.; Hubbard, G. B.; Ikeno, Y.; Ruddle, N. H.; Schultz, J. L.; Dixit, V. D.

doi:10.1101/607192

bioRxiv · 10.1101/607192

Aging induces Nlrp3 inflammasome dependent adipose B cell expansion to impair metabolic homeostasis

Camell, C. D.·Lee, A.·Günther, P.·Goldberg, E. L.·Spadaro, O.·Youm, Y.-H.·Bartke, A.·Hubbard, G. B.·Ikeno, Y.·Ruddle, N. H.·Schultz, J. L.·Dixit, V. D.

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Abstract

Visceral adiposity in elderly is associated with alterations in adipose tissue immune cells leading to inflammation and metabolic dysfunction. The Nlrp3 inflammasome is a critical regulator of macrophage activation, inflammation, and immunometabolism in visceral adipose tissue during aging; however, the potential contribution of adipose tissue B cells is unexplored. Here, we show that aging expands adipose-resident B cells and fat-associated lymphoid clusters (FALCs) in visceral white adipose tissue. Adipose tissue B cells exhibit a memory-like B cell profile similar to the phenotype of aged B cells that are increased in spleen of old mice. Mechanistically, the age-induced FALC formation and adipose B cell expansion, but not B cell transcriptional program, is dependent on the Nlrp3 inflammasome. Furthermore, B cell depletion in aged mice restores lipolysis and defense against loss of core body temperature during cold stress. These data reveal that inhibiting Nlrp3-dependent B cell accumulation can be targeted to reverse metabolic impairment in aging adipose tissue.\n\nHighlights- Adipose-resident aged B cells are increased in fat-associated lymphoid clusters (FALC)\n\n- FALC formation and adipose-resident B cell expansion during aging are regulated by the Nlrp3 inflammasome\n\n- Nlrp3 and B cell depletion in aging restores lipolysis and improves cold tolerancea

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Camell, C. D., Lee, A., Günther, P., Goldberg, E. L., Spadaro, O., Youm, Y.-H., Bartke, A., Hubbard, G. B., Ikeno, Y., Ruddle, N. H., Schultz, J. L., Dixit, V. D.. 2019-04-13. Aging induces Nlrp3 inflammasome dependent adipose B cell expansion to impair metabolic homeostasis. https://doi.org/10.1101/607192

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