Depletion of CD40 on CD11c⁺ cells worsens the metabolic syndrome and ameliorates hepatic inflammation during NASH.

ABSTRACT: The co-stimulatory CD40-CD40L dyad plays a central role in fine-tuning immune reactions, including obesity-induced inflammation. Genetic ablation of CD40L reduced adipose tissue inflammation, while absence of CD40 resulted in aggravated metabolic dysfunction in mice. During obesity, CD40 expressing CD11c⁺ dendritic cells (DC) and macrophages accumulate in adipose tissue and liver. We investigated the role of CD40⁺CD11c⁺ cells in the metabolic syndrome and nonalcoholic steatohepatitis (NASH). DC-CD40-ko mice (CD40^fl/flCD11c^cre) mice were subjected to obesity or NASH. Obesity and insulin resistance were induced by feeding mice a 54% high fat diet (HFD). NASH was induced by feeding mice a diet containing 40% fat, 20% fructose and 2% chole

SUBMITTER: Aarts S 

PROVIDER: S-EPMC6789104 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature