Conventional type 1 dendritic cells protect against age-related adipose tissue dysfunction and obesity

Abstract

Conventional dendritic cells (cDCs) scan and integrate environmental cues in almost every tissue, including exogenous metabolic signals. While cDCs are critical in maintaining immune balance, their role in preserving energy homeostasis is unclear. Here, we showed that Batf3-deficient mice lacking conventional type 1 DCs (cDC1s) had increased body weight and adiposity during aging. This led to impaired energy expenditure and glucose tolerance, insulin resistance, dyslipidemia, and liver steatosis. cDC1 deficiency caused adipose tissue inflammation that was preceded by a paucity of NK1.1+ invariant NKT (iNKT) cells. Accordingly, among antigen-presenting cells, cDC1s exhibited notable induction of IFN-γ production by iNKT cells, which plays a metabolically protective role in lean adipose tissue. Flt3L treatment, which expands the dendritic cell (DC) compartment, mitigated diet-induced obesity and hyperlipidemia in a Batf3-dependent manner. This effect was partially mediated by NK1.1+ cells. These results reveal a new critical role for the cDC1-iNKT cell axis in the regulation of adipose tissue homeostasis.

Antiviral State of CD1c+ cDC contributes to Increased Maturation and Activation of Cytotoxic Natural Killer cells in Sjögren’s Syndrome

“…Importantly, high MICAB expression has been observed in SGs from pSS, 48 and polymorphism of this molecule have been linked to higher susceptibility to develop the disease, 49 . In addition, some of our data suggest that CD141+ and CD1c+ cDC might provide non-redundant signals to NK cells since we have shown that CD141+ cDC might be more effective inducing IFNg expression on NK cells or efficiently activate CD8+ T cells, as previously reported, 26, 27, 50 5, 6 . Therefore, further studies are required to better understand complex interactions between different DC subsets contributing to pSS pathology.…”

BATF3 Protects Against Metabolic Syndrome and Maintains Intestinal Epithelial Homeostasis

“…A recent study investigated the role of BATF3 and cDC1s in the regulation of adipose tissue homeostasis ( 99 ). The authors demonstrate that the abundance of cDC1s in visceral fat tissue is reduced in HFD fed mice and that BATF3-deficiency and the loss of cDC1 results in the development of obesity during ageing.…”

Anti-Inflammatory Mechanisms of Dietary Flavones: Tapping into Nature to Control Chronic Inflammation in Obesity and Cancer

“…Mice lacking DC, due to the ablation of Flt3l or E2-2 genes, did not develop insulin resistance when fed with a high-fat diet (HFD) [ 60 , 61 ]. However, ablation of the Batf3 gene, which results in the lack of conventional DC, led to the development of insulin resistance and increased adiposity [ 62 ]. These controversial findings warrant further studies to delineate the role of specific DC populations in obesity.…”