Distinct metabolic states guide maturation of inflammatory and tolerogenic dendritic cells

Abstract

Cellular metabolism underpins immune cell functionality, yet our understanding of metabolic influences in human dendritic cell biology and their ability to orchestrate immune responses is poorly developed. Here, we map single-cell metabolic states and immune profiles of inflammatory and tolerogenic monocytic dendritic cells using recently developed multiparametric approaches. Single-cell metabolic pathway activation scores reveal simultaneous engagement of multiple metabolic pathways in distinct monocytic dendritic cell differentiation stages. GM-CSF/IL4-induce rapid reprogramming of glycolytic monocytes and transient co-activation of mitochondrial pathways followed by TLR4-dependent maturation of dendritic cells. Skewing of the mTOR:AMPK phosphorylation balance and upregulation of OXPHOS, glycolytic and fatty acid oxidation metabolism underpin metabolic hyperactivity and an immunosuppressive phenotype of tolerogenic dendritic cells, which exhibit maturation-resistance and a de-differentiated immune phenotype marked by unique immunoregulatory receptor signatures. This single-cell dataset provides important insights into metabolic pathways impacting the immune profiles of human dendritic cells.

Metabolic sensor AMPK licenses CD103+dendritic cells to induce Treg responses

“…Most studies interrogating the metabolic properties of human tolDCs have been focused on moDCs treated with VitD3 alone or in conjunction with Dex. Consistent with these earlier reports (Adamik et al, 2022; Ferreira et al, 2015; Vanherwegen et al, 2018; Malinarich et al, 2015), we find VitD3-DCs to display strong metabolic reprogramming with both features of anabolism and catabolism, whereas Dex-DCs showed relatively modest metabolic changes. On the other hand, there have been no detailed investigations into the metabolic properties of RA-DCs.…”

Strategies to overcome DC dysregulation in the tumor microenvironment

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Tr1 cell-mediated protection against autoimmune disease by intranasal administration of a fusion protein targeting cDC1 cells

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