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Adipose cDC1s contribute to obesity-associated white adipose tissue inflammation and metabolic dysfunction through STING-dependent IL-12 production

ABSTRACT: Obesity is associated with chronic low-grade white adipose tissue (WAT) inflammation that can contribute to the development of insulin resistance in mammals. Previous studies have identified interleukin (IL)-12 as a critical upstream regulator of WAT inflammation and metabolic dysfunction during obesity, however, the cell types and mechanisms that initiate WAT IL-12 production remain unclear. Analysis of mouse and human WAT single cell transcriptomic datasets, IL-12 reporter mice, and IL-12p70 protein levels by ELISA identified activated conventional type 1 dendritic cells (cDC1s) as the cellular source of WAT IL-12 during diet-induced obesity. cDC1s were required for the development of obesity-associated inflammation by increasing group 1 innate lymphocyte interferon (IFN)-γ production and inflammatory macrophage accumulation. Inducible depletion of cDC1s increased WAT insulin sensitivity and systemic glucose tolerance during diet-induced obesity. Endocytosis of apoptotic bodies containing self-DNA by WAT cDC1 drove STING-dependent IL-12 production. Together, these results suggest that WAT cDC1s act as critical regulators of adipose tissue inflammation and metabolic homeostasis during obesity.

ORGANISM(S): Mus musculus

PROVIDER: GSE236110 | GEO | 2024/06/30

REPOSITORIES: GEO

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Adipose cDC1s contribute to obesity-associated white adipose tissue inflammation and metabolic dysfunction through STING-dependent IL-12 production

Project description:Adipose cDC1s contribute to obesity-associated white adipose tissue inflammation and metabolic dysfunction through STING-dependent IL-12 production

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