Metabolic regulation of dendritic cell function 3730

Description Dendritic cells are professional and potent antigen presenting cells that screen all tissues for antigens, infection agents, and tumor cells to prime and activate T cells during immune responses. Dendritic cells are required for efficient recognition and elimination of infected and tumor cells, but they also can amplify pathological inflammation in autoimmunity and allergic responses leading to tissue damage. How dendritic cells balance inflammatory and anti-inflammatory programs remains largely unknown. We and others have shown that dendritic cells metabolism has a profound impact on antigen presentation and inflammation. We showed that excessive fatty acid metabolism increases chronic inflammation driven by dendritic cells in models of skin inflammation in obesity. This metabolic reprogramming of dendritic cells initiated the unfolded protein stress response and targeted stress-activated transcription factors to amplify the expression of pro-inflammatory cytokines. We also found that glutamine metabolism of dendritic cells directly regulates antigen presentation and cytokine secretion through the mechanism involving the conversion of glutamine to glutamate by mitochondrial glutaminase. Glutaminase-dependent metabolism of dendritic cells enhanced autophagy and autophagy-dependent antigen presentation to CD4 T cells, thus linking metabolic sensing to immunity. These results show that metabolism is an integral regulator of immune functions of dendritic cells. Funding Sources Supported by NIH/NIAMS R21AR080233; Glenn Foundation for Medical Research and AFAR Grant for Junior Faculty; Discovery Grant from The National Psoriasis Foundation (USA) Topic Categories Antigen and Dendritic Cell Processing, Presentation, and Biology (AGDC)