What do dendritic cells differentiate from

Pulmonary dendritic cells producing IL mediate toerance induced by respiratory exposure to antigen. Hart, D. Dendritic cells: unique leukocyte populations which control the primary immune response. Blood 90 , — The origin and kinetics of mononuclear phagocytes.

Inaba, K. Granulocytes, macrophages, and dendritic cells arise from a common major histocompatibility complex class II-negative progenitor in mouse bone marrow.

Natl Acad. USA 90 , — Sallusto, F. The first report to describe the generation of DCs from human monocytes in vitro in the presence of granulocyte—macrophage colony-stimulating factor GM-CSF and interleukin-4 IL—4. Randolph, G. Differentiation of phagocytic monocytes into lymph node dendritic cells in vivo. Immunity 11 , — Thymic dendritic cells and T cells develop simultaneously in the thymus from a common precursor population. Nature , — A description of thymic DCs that are derived from CD4 low early thymic precursors and are devoid of myeloid-reconstitution potential.

This led to the concept that some DCs could be of lymphoid origin. Wu, L. Thymic dendritic cell precursors: relationship to the T lymphocyte lineage and phenotype of the dendritic cell progeny.

Cell-autonomous defects in dendritic cell populations of Ikaros mutant mice point to a developmental relationship with the lymphoid lineage. Immunity 7 , — Immunity 9 , — Traver, D. Science , — Manz, M. Dendritic cell potentials of early lymphoid and myeloid progenitors. Blood 97 , — Development of thymic and splenic dendritic cell populations from different hemopoietic precursors. Blood 98 , — D'Amico, A.

The early progenitors of mouse dendritic cells and plasmacytoid pre-dendritic cells are within the bone marrow hemopoietic precursors expressing FLT3. Corcoran, L. The lymphoid past of mouse plasmacytoid cells and thymic dendritic cells. Hacker, C. Transcriptional profiling identifies Id2 function in dendritic cell develoment. Georgopoulos, K.

The Ikaros gene is required for the development of all lymphoid lineages. Cell 79 , — Rodewald, H. Developmental dissociation of thymic dendritic cell and thymocyte lineages revealed in growth factor receptor mutant mice.

USA 96 , — Radtke, F. Notch1 deficiency dissociates the intrathymic development of dendritic cells and T cells. Guerriero, A. Blood 95 , — Anderson, K. Transcription factor PU. Aliberti, J. Schiavoni, G. Zhang, Y. Blood 92 , — Merad, M. Brasel, K. Generation of murine dendritic cells from flt3-ligand-supplemented bone marrow cultures. References 39 and 40 describe the differentiation of DCs from bone-marrow cultures in the presence of fms-related tyrosine kinase 3 ligand FLT3L , representing an alternative culture method for the generation of DCs that are similar to those found in vivo , including plasmacytoid-like DCs.

Brawand, P. Murine plasmacytoid pre-dendritic cells generated from FLT3 ligand-supplemented bone marrow cultures are immature APCs. Gilliet, M. Boonstra, A. Flexibility of mouse classical and plasmacytoid-derived dendritic cells in directing T helper type 1 and 2 cell development: dependency on antigen dose and differential Toll-like receptor ligation.

Origin and differentiation of dendritic cells. McKenna, H. Mice lacking flt3 ligand have deficient hematopoiesis affecting hematopoietic progenitor cells, dendritic cells, and natural killer cells. Borkowski, T. Five weeks of Se-deficient diet treatment can decrease the epidermal Langerhans cell numbers by half in mice The role of Se during DC differentiation has also been studied in chicken.

Addition of inorganic Se sodium selenite in the culture system was reported to accelerate the differentiation of chicken DCs from chicken peripheral blood monocytes Studies above pointed out diverse effect of vitamins, amino acids and selenium on DC development. Other nutrients were also reported to have important effect on function or survival of DC. Whether other nutrients influence differentiation of DCs awaits further study.

Distinct tissue resident DC subsets with different functions are regulated by different tissue environments. Metabolic environment in different tissues may significantly impact the differentiation of pre-DCs to resident DC subsets. For example, in lung the cells have better access to oxygen in adipose tissue the fatty acid metabolism is more active, whereas in intestine, the metabolism of various carbohydrates, peptides and small nutrients are highly active.

Intestinal DCs, for instance, are among the first line of immune cells that encounter dietary nutrients, thus, it is highly possible that these nutrients function as major regulators in the differentiation of intestinal DC from pre-DCs.

Based on the finding that retinoic acid was involved in regulation of intestinal DC differentiation 73 , 74 , as well as the study showing that gut microbiota-derived short chain fatty acids could serve as competitive regulators for intestinal DC differentiation 86 , 87 , it is reasonable to assume that homeostasis of tissue resident DC subsets may also be susceptible to distinct metabolic pathways in other tissues.

Further exploration of the exact roles of different metabolites and nutrients in the differentiation of different tissue resident DCs should provide new knowledge for better understanding the importance of metabolic regulation of DC differentiation and function, and the potential correlations between immune alterations and some metabolic diseases. In recent years, emerging evidence has revealed that the metabolic modulation is essential for the development and function of immune system.

Some evidence also suggested that the differentiation and activation of DCs might also be under metabolic modulation. A better understanding of the metabolic regulation of DC development and differentiation will not only help to establish the crucial network amongst various molecular regulatory mechanisms and metabolic regulations, but also help to elucidate the potential association of altered DC differentiation and activation with some metabolic diseases.

However, current knowledge in this field is still limited. In this review we summarized these findings from published studies as shown in Figure 1. As reviewed by O'Neill et al.

However, only few inhibitors were tested to determine the roles of metabolic regulation in DC differentiation. Most of the published studies were done with the in vitro culture systems supplemented with Flt3L or GM-CSF, although they provided useful information for these mentioned metabolic pathways in DC differentiation, clear and definitive conclusions can only be drawn from properly designed in vivo studies, and those should be the major focus of the further studies.

The impacts of other metabolic pathways including the pentose phosphate pathway PPP and nitrogen metabolism pathways on DC differentiation are yet to be determined. In addition, apart from the mTOR pathway, the effects of other molecular signaling pathways that regulate metabolism such as AMPK pathway on DC differentiation are not yet clearly elucidated.

The role of other nutrients including minerals in DC differentiation also needs more attention for their easy access in daily diets. Immunotherapy has shown a bright future for cancer treatment. The functions of DCs are crucial for the effectiveness of these therapies. Impairment of DC homeostasis or function are related to many diseases, such as inflammatory diseases 89 , 90 , autoimmune diseases 91 and cancer 92 — The DC vaccines also hold a promising potential for developing more effective approaches for the treatment of various immune related diseases.

The in vitro generation of various DC subsets from hematopoietic progenitor cells is non-substitutable in the studies of human DC differentiation. Modulation of specific metabolic pathways or addition of particular nutrients during the generation of DCs according to their metabolism requirements, may help to obtain specific DC subsets desired for various clinical applications. More extensive studies of the metabolic regulation of DC development and differentiation should be one of the priorities in the field of DC biology and the new knowledge gained from these studies will facilitate the clinical applications of DCs in the treatment of some immune-related diseases.

LW supervised the writing, analyzed, and edited this manuscript. ZH wrote, organized and edited the manuscript. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. National Center for Biotechnology Information , U. Journal List Front Immunol v. Front Immunol.

Published online Mar Author information Article notes Copyright and License information Disclaimer. Reviewed by: Hongbo Chi, St. Received Sep 15; Accepted Feb 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. This article has been cited by other articles in PMC. Abstract Dendritic cells DCs are important antigen-presenting cells APCs that play essential roles in bridging innate and adaptive immune responses.

Keywords: dendritic cell DC , cell differentiation, metabolic regulation, glycolysis, fatty acid FA , mitochondria function, mTOR pathway, nutrients. Table 1 Murine and human dendritic cell subsets are outlined with their surface phenotype, major transcription factors required for their development and their main functions 7 — Open in a separate window. Figure 1. Role of Glycolysis and Mitochondria Function Glycolysis is one of the most important components in glucose metabolism which converts glucose into pyruvate in the cytoplasm.

Role of Fatty Acid Metabolism Fatty acids can also serve as fuel for energy production in many types of cells Role of Mammalian Target of Rapamycin mTOR The mTOR pathway responds to various environmental cues such as nutrients and growth factors and controls numerous cellular processes that related to cell growth and metabolism. Amino Acids Amino acids as important components of proteins also take part in many metabolic processes.

Dietary Minerals Selenium Se is an essential micronutrient that is important for metabolism process like proper thyroid hormone metabolism and has non-negligible effects on the immune system through its incorporation into selenoproteins.

Discussion and Conclusion In recent years, emerging evidence has revealed that the metabolic modulation is essential for the development and function of immune system. Author Contributions LW supervised the writing, analyzed, and edited this manuscript. Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Footnotes Funding. References 1. Shortman K, Liu YJ. Mouse and human dendritic cell subtypes. Nat Rev Immunol. Development of antigen cross-presentation capacity in dendritic cells. Trends Immunol. Mildner A, Jung S. Development and function of dendritic cell subsets. Development of conventional dendritic cells: from common bone marrow progenitors to multiple subsets in peripheral tissues. Mucosal Immunol.

Zhou H, Wu L. The development and function of dendritic cell populations and their regulation by miRNAs. Protein Cell. Seillet C, Belz GT.

Terminal differentiation of dendritic cells. Adv Immunol. Transcriptional control of dendritic cell development. Ann Rev Immunol. The cell surface phenotype of human dendritic cells. Semin Cell Dev Biol. Dendritic cell subsets.

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