Glutaminase is a novel immunometabolic regulator of dendritic cell functions 2478

Abstract Description Dendritic cells have been shown to use glutamine to enhance antigen presentation to T cells. However, it remains unknown if the metabolization of glutamine dictates the immune functions of dendritic cells and contributes to antigen presentation and inflammation. We found that glutaminase (GLS), a rate-limiting mitochondrial enzyme converting glutamine into glutamate, in dendritic cells increases antigen presentation to CD4 T cells and cytokine secretion in vitro. GLS-deficient dendritic cells showed similar antigen uptake and processing, however, they failed to fully activate CD4 T cell proliferation in an autophagy-dependent manner. Moreover, GLS activity increased IL-6 and IL-12 secretion, enhanced IFNγ receptor signaling, and increased H3 histone acetylation during activation of dendritic cells. We found a distinct subset of GLS-expressing dendritic cells abundant in multiple tissues in mice, including healthy and inflamed skin and draining lymph nodes. These results show for the first time that GLS-dependent glutamine metabolism can act as a direct regulator of inflammation and antigen presentation, linking metabolic sensing to dendritic cell function. We suggest GLS-mediated glutaminolysis in dendritic cells can be pro-immunogenic and might drive the progression and exacerbation of chronic skin inflammatory diseases. Funding Sources R21 AR080233 NIAMS NIH grant Topic Categories Antigen and Dendritic Cell Processing, Presentation, and Biology (AGDC)