Lipid metabolism in dendritic cell biology

Abstract

SummaryDendritic cells (DCs) are innate immune cells that detect and process environmental signals and communicate them with T cells to bridge innate and adaptive immunity. Immune signals and microenvironmental cues shape the function of DC subsets in different contexts, which is associated with reprogramming of cellular metabolic pathways. In addition to integrating these extracellular cues to meet bioenergetic and biosynthetic demands, cellular metabolism interplays with immune signaling to shape DC‐dependent immune responses. Emerging evidence indicates that lipid metabolism serves as a key regulator of DC responses. Here, we summarize the roles of fatty acid and cholesterol metabolism, as well as selective metabolites, in orchestrating the functions of DCs. Specifically, we highlight how different lipid metabolic programs, including de novo fatty acid synthesis, fatty acid β oxidation, lipid storage, and cholesterol efflux, influence DC function in different contexts. Further, we discuss how dysregulation of lipid metabolism shapes DC intracellular signaling and contributes to the impaired DC function in the tumor microenvironment. Finally, we conclude with a discussion on key future directions for the regulation of DC biology by lipid metabolism. Insights into the connections between lipid metabolism and DC functional specialization may facilitate the development of new therapeutic strategies for human diseases.

Cystatin from the helminth Ascaris lumbricoides upregulates mevalonate and cholesterol biosynthesis pathways and immunomodulatory genes in human monocyte-derived dendritic cells

“…Lipid metabolism is crucial in DCs maturation and activation; changes in this process can alter DCs function and in some instances induce tolerogenic cells ( 58 ). For example, accumulation of intracellular oxidized lipids (cholesterol, triglycerides, and fatty acids) induced by tumor-derived factors impacts antigen presentation in human moDCs and mouse DCs ( 59 , 60 ).…”

The novel mechanism facilitating chronic hepatitis B infection: immunometabolism and epigenetic modification reprogramming

“…Cholesterol stands as an essential lipid molecule intricately involved in pivotal biological processes, encompassing lipid rafts and major histocompatibility complex (MHC) molecules ( 130 ). Strategies aimed at increasing cholesterol accumulation on DCs can enhance antigen presentation, thus improving the efficacy of therapeutic vaccines and rescuing the exhausted HBV-specific CD8 + T cells ( 129 ).…”

SLC38A2 and glutamine signalling in cDC1s dictate anti-tumour immunity

“…Notably, similar to FLCN deficiency, SLC38A2 deficiency in DCs eliminates the anti-tumour effect of glutamine supplementation, thereby establishing this glutamine transporter and FLCN signalling as critical drivers of cDC1 function and tumour immunity. Our work provides important insights into the immunostimulatory effects of glutamine in DCs, which contrast with the immunosuppressive or tolerogenic effects of lipids and indoleamine 2,3-dioxygenase 1-mediated tryptophan catabolism in modulating DC functions in tumours or inflammatory settings [48][49][50] . Collectively, targeting glutamine levels in tumours or glutamine-dependent signalling in cDC1s has implications for improving cancer treatments and overcoming tumour-mediated immunosuppression.…”