Interleukin-10 expressing B lineage cells in visceral adipose tissue protect against aging-related insulin resistance and extend lifespan.

Abstract

Visceral adipose tissue (VAT) inflammation is considered as an important contributor of aging, however, whether there is endogenous factor(s) in VAT that counteract this process remains obscure. Here we reported that interleukin (IL)-10 expressing B lineage (B-10) cells are greatly expanded in aged VAT in human and mouse. In aged VAT, B-10 cells are the primary source of IL-10. B cell-specific knockout of IL-10 exaggerated aging-related inflammation and insulin resistance (IR) and reduced lifespan, which could be partially recovered via adoptive transfer of B-10 cells from wild-type mice. Aged VAT microenvironment enhanced IL-10 secretion and proliferation of B-10 cells. The proliferation of B-10 cells was mediated by increases in BAFF in aged VAT. Knock-down of BAFF in VAT compromised aging-related expansion of B-10 cells. On the contrary, VAT-specific overexpression of BAFF promoted B-10 cells expansion, improved aging-related inflammation and IR, and prolonged lifespan.