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      Metabolic Regulation of Dendritic Cell Differentiation

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          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.

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          Dendritic Cells and Cancer Immunity.

          Dendritic cells (DCs) are central regulators of the adaptive immune response, and as such are necessary for T-cell-mediated cancer immunity. In particular, antitumoral responses depend on a specialized subset of conventional DCs that transport tumor antigens to draining lymph nodes and cross-present antigen to activate cytotoxic T lymphocytes. DC maturation is necessary to provide costimulatory signals to T cells, but while DC maturation occurs within tumors, it is often insufficient to induce potent immunity, particularly in light of suppressive mechanisms within tumors. Bypassing suppressive pathways or directly activating DCs can unleash a T-cell response, and although clinical efficacy has proven elusive, therapeutic targeting of DCs continues to hold translational potential in combinatorial approaches.
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            Mouse and human dendritic cell subtypes.

            Dendritic cells (DCs) collect and process antigens for presentation to T cells, but there are many variations on this basic theme. DCs differ in the regulatory signals they transmit, directing T cells to different types of immune response or to tolerance. Although many DC subtypes arise from separate developmental pathways, their development and function are modulated by exogenous factors. Therefore, we must study the dynamics of the DC network in response to microbial invasion. Despite the difficulty of comparing the DC systems of humans and mice, recent work has revealed much common ground.
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              Metabolism of stromal and immune cells in health and disease.

              Cancer cells have been at the centre of cell metabolism research, but the metabolism of stromal and immune cells has received less attention. Nonetheless, these cells influence the progression of malignant, inflammatory and metabolic disorders. Here we discuss the metabolic adaptations of stromal and immune cells in health and disease, and highlight how metabolism determines their differentiation and function.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                13 March 2019
                2019
                : 10
                : 410
                Affiliations
                [1] 1School of Medicine, Institute for Immunology, Tsinghua University , Beijing, China
                [2] 2Tsinghua-Peking Center for Life Science , Beijing, China
                Author notes

                Edited by: Bart Everts, Leiden University Medical Center, Netherlands

                Reviewed by: Hongbo Chi, St. Jude Children's Research Hospital, United States; Leonard Pelgrom, Leiden University Medical Center, Netherlands

                *Correspondence: Li Wu wuli@ 123456mail.tsinghua.edu.cn

                This article was submitted to Antigen Presenting Cell Biology, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2019.00410
                6424910
                30930893
                df3ef7a5-dde7-4e51-be76-be474ce77153
                Copyright © 2019 He, Zhu, Shi, Wu and Wu.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 15 September 2018
                : 15 February 2019
                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 94, Pages: 10, Words: 7713
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: No. 31330027
                Award ID: No. 91642207
                Funded by: Ministry of Science and Technology of the People's Republic of China 10.13039/501100002855
                Award ID: No. 2015CB943200
                Categories
                Immunology
                Mini Review

                Immunology
                dendritic cell (dc),cell differentiation,metabolic regulation,glycolysis,fatty acid (fa),mitochondria function,mtor pathway,nutrients

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