Abstract
Dendritic cells (DCs) are important antigen-presenting cells (APCs) that play essential roles in bridging innate and adaptive immune responses. Differentiation stages of DC subsets from bone marrow progenitor cells have been well-defined during the past decades. Features that distinguish DC progenitor cells from each differentiation stages, related signaling pathways and transcription factors that are crucial for DC lineage commitment have been well-elucidated in numerous studies. Recently, growing evidence are showing that cellular metabolism, as one of the most fundamental process of cells, has essential role in the modulation of immune system. There have been multiple reports and reviews that focus on the metabolic modulations on DC functions, however little attention had been paid to the metabolic regulation of DC development and differentiation. In recent years, increasing evidence suggests that metabolic regulations also exert significant impact on DC differentiation, as well as on the homeostasis of tissue resident DCs. The focus of this review is to summarize the findings from recent studies on the metabolic regulation of DC differentiation and to discuss the impacts of the three major aspects of metabolism on the processes of DC development and differentiation, namely the changes in metabolic pathways, the molecular signaling pathways that modulate cell metabolism, and the effects of metabolites and nutrients. The aim of this review is to draw attentions to this important and exciting research field where the effects of metabolic process and their regulation in DC differentiation need to be further explored.
Highlights
Dendritic cells (DCs) are specialized cells that recognize the pathogens by the various pattern recognition receptors (PRRs) and initiate the innate immune response, and can uptake, process and present antigens to naïve T cells, promote the activation of adaptive immune response [1]
common DC progenitors (CDPs) differentiate into pre-conventional DCs (cDCs) and pre-plasmacytoid DCs (pDCs), and pre-pDCs further differentiate into pDCs
Human granulocyte macrophage progenitors (GMP) can be divided into three sub-populations, based on their differentiation potential determined by clonal analysis at single cell level: one give rise to granulocyte, monocyte and DCs, defined as hGMDP, which is equivalent to murine common myeloid progenitors (CMPs); one produce monocytes and DCs, defined as hMDP; the hCDP subpopulation can only differentiate into DC subsets, equivalent to murine CDP [20, 21]
Summary
Specialty section: This article was submitted to Antigen Presenting Cell Biology, a section of the journal Frontiers in Immunology. Dendritic cells (DCs) are important antigen-presenting cells (APCs) that play essential roles in bridging innate and adaptive immune responses. Growing evidence are showing that cellular metabolism, as one of the most fundamental process of cells, has essential role in the modulation of immune system. In recent years, increasing evidence suggests that metabolic regulations exert significant impact on DC differentiation, as well as on the homeostasis of tissue resident DCs. The focus of this review is to summarize the findings from recent studies on the metabolic regulation of DC differentiation and to discuss the impacts of the three major aspects of metabolism on the processes of DC development and differentiation, namely the changes in metabolic pathways, the molecular signaling pathways that modulate cell metabolism, and the effects of metabolites and nutrients.
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