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The EMBO Journal Jun 2003Dendritic cells are professional antigen-presenting cells able to initiate innate and adaptive immune responses against invading pathogens. In response to external... (Review)
Review
Dendritic cells are professional antigen-presenting cells able to initiate innate and adaptive immune responses against invading pathogens. In response to external stimuli dendritic cells undergo a complete genetic reprogramming that allows them to become, soon after activation, natural killer cell activators and subsequently T cell stimulators. The recent observation that dendritic cells produce interleukin 2 following microbial stimulation opens new possibilities for understanding the efficiency of dendritic cells in regulating immune system functions. This review discusses how dendritic cells control natural killer, T- and B-cell responses and the relevance of interleukin 2 in these processes.
Topics: Animals; B-Lymphocytes; Cell Communication; Cell Differentiation; Dendritic Cells; Humans; Immunity, Innate; Interleukin-2; Killer Cells, Natural; Models, Immunological; T-Lymphocytes
PubMed: 12773371
DOI: 10.1093/emboj/cdg261 -
Frontiers in Immunology 2018Dendritic cells (DCs) are the most potent antigen presenting cells and possess an incomparable ability to activate and instruct T cells, which makes them one of the...
Dendritic cells (DCs) are the most potent antigen presenting cells and possess an incomparable ability to activate and instruct T cells, which makes them one of the cornerstones in the regulation of the cross-talk between innate and adaptive immunity. Therefore, a deep understanding of DC biology lays the foundations to describe and to harness the mechanisms that regulate the development of the adaptive response, with clear implications in a vast array of fields such as the study of autoimmune diseases and the development of new vaccines. However, the great difficulty to obtain large quantities of viable non-activated DCs for experimentation have considerably hindered the progress of DC research. Several strategies have been proposed to overcome these limitations by promoting an increase of DC abundance , by inducing DC development from DC progenitors and by generating stable DC lines. In the past years, we have described a method to derive immortalized stable DC lines, named MutuDCs, from the spleens of Mushi1 mice, a transgenic mouse strain that express the simian virus 40 Large T-oncogene in the DCs. The comparison of these DC lines with the vast variety of DC subsets described has shown that all the MutuDC lines that we have generated so far have phenotypic and functional features of type 1 conventional DCs (cDC1s). With the purpose of deriving DC lines with characteristics of type 2 conventional DCs (cDC2s), we bred a new Batf3 Mushi1 murine line in which the development of the cDC1 subset is severely defective. The new MutuDC line that we generated from Batf3 Mushi1 mice was phenotypically and functionally characterized in this work. Our results demonstrated that all the tested characteristics of this new cell line, including the expression of subset-determining transcription factors, the profile of cytokine production and the ability to present antigens, are comparable with the features of splenic CD4 cDC2s. Therefore, we concluded that our new cell line, that we named CD4 MutuDC2 line, represents a valuable model for the CD4 cDC2 subset.
Topics: Adaptive Immunity; Animals; Cell Line; Dendritic Cells; Mice; Mice, Knockout; Spleen
PubMed: 30197645
DOI: 10.3389/fimmu.2018.01912 -
Cellular Physiology and Biochemistry :... 2014Dendritic cells (DCs) are the cutting edge in innate and adaptive immunity. The major functions of these antigen-presenting cells are the capture, endosomal processing... (Review)
Review
Dendritic cells (DCs) are the cutting edge in innate and adaptive immunity. The major functions of these antigen-presenting cells are the capture, endosomal processing and presentation of antigens, providing them an exclusive ability to provoke adaptive immune responses and to induce and control tolerance. Immature DCs capture and process antigens, migrate towards secondary lymphoid organs where they present antigens to naive T cells in a well-synchronized sequence of procedures referred to as maturation. Indeed, recent research indicated that sphingolipids are modulators of essential steps in DC homeostasis. It has been recognized that sphingolipids not only modulate the development of DC subtypes from precursor cells but also influence functional activities of DCs such as antigen capture, and cytokine profiling. Thus, it is not astonishing that sphingolipids and sphingolipid metabolism play a substantial role in inflammatory diseases that are modulated by DCs. Here we highlight the function of sphingosine 1-phosphate (S1P) on DC homeostasis and the role of S1P and S1P metabolism in inflammatory diseases.
Topics: Adaptive Immunity; Animals; Antigens; Cytokines; Dendritic Cells; Humans; Immunity, Innate; Lysophospholipids; Skin Diseases; Sphingosine; Toll-Like Receptors; Transcriptome
PubMed: 24977479
DOI: 10.1159/000362982 -
Cellular & Molecular Immunology Apr 2004The dendritic cell system contains conventional dendritic cells (DCs) and plasmacytoid pre-dendritic cells (pDCs). Both DCs and pDCs are bone marrow derived cells.... (Review)
Review
The dendritic cell system contains conventional dendritic cells (DCs) and plasmacytoid pre-dendritic cells (pDCs). Both DCs and pDCs are bone marrow derived cells. Although the common functions of DCs are antigen-processing and T-lymphocyte activation, they differ in surface markers, migratory patterns, and cytokine output. These differences can determine the fate of the T cells they activate. Several subsets of mature DCs have been described in both mouse and human and the developmental processes of these specialized DC subsets have been studied extensively. The original concept that all DCs were of myeloid origin was questioned by several recent studies, which demonstrated that in addition to the DCs derived from myeloid precursors, some DCs could also be efficiently generated from lymphoid-restricted precursors. Moreover, it has been shown recently that both conventional DCs and pDCs can be generated by the Flt3 expressing hemopoietic progenitors regardless of their myeloid- or lymphoid-origin. These findings suggest an early developmental flexibility of precursors for DCs and pDCs. This review summarizes some recent observations on the development of DC system in both human and mouse.
Topics: Animals; Antigens, CD; Cell Differentiation; Dendritic Cells; Hematopoietic Stem Cells; Humans; Lymphoid Tissue; Phenotype
PubMed: 16212897
DOI: No ID Found -
Frontiers in Immunology 2019Dendritic cells (DC) are a diverse group of leukocytes responsible for bridging innate and adaptive immunity. Despite their functional versatility, DCs exist primarily... (Review)
Review
Dendritic cells (DC) are a diverse group of leukocytes responsible for bridging innate and adaptive immunity. Despite their functional versatility, DCs exist primarily in two basic functional states: immature and mature. A large body of evidence suggests that upon interactions with pathogens, DCs undergo intricate cellular processes that culminate in their activation, which is paramount to the orchestration of effective immune responses against a parasites. Herein we offer a concise review of the emerging hallmarks of DCs activation in leishmaniasis as well as a comprehensive discussion of the following underlying molecular events: DC- interaction, antigen uptake, costimulatory molecule expression, parasite ability to affect DC migration, antigen presentation, metabolic reprogramming, and epigenetic alterations.
Topics: Adaptive Immunity; Animals; Antigen Presentation; Cell Movement; Dendritic Cells; Epigenesis, Genetic; Humans; Leishmaniasis; Mice; Receptors, Purinergic; Toll-Like Receptors
PubMed: 30873156
DOI: 10.3389/fimmu.2019.00227 -
Virulence Nov 2012The application of advanced imaging techniques to fundamental questions in immunology has provided insight into dendritic cell function and has challenged dogma created... (Review)
Review
The application of advanced imaging techniques to fundamental questions in immunology has provided insight into dendritic cell function and has challenged dogma created using static imaging of lymphoid tissue. The history of dendritic cell biology has a storied past and is tightly linked to imaging. The development of imaging techniques that emphasize live cell imaging in situ has provided not only breath-taking movies, but also novel insights into the importance of spatiotemporal relationships between antigen presenting cells and T cells. This review serves to provide a primer on two-photon microscopy, TIRF microscopy, spinning disk confocal microscopy and optical trapping and provides selective examples of insights gained from these tools on dendritic cell biology.
Topics: Animals; Dendritic Cells; Humans; Image Processing, Computer-Assisted; Microscopy; Optical Tweezers
PubMed: 23221474
DOI: 10.4161/viru.22981 -
Microbes and Infection Feb 2011Brucella can parasitize within human antigen-presenting cells modifying phagocytosis, phagolysosome fusion, antigen presentation, cytokine secretion, and apoptosis.... (Review)
Review
Brucella can parasitize within human antigen-presenting cells modifying phagocytosis, phagolysosome fusion, antigen presentation, cytokine secretion, and apoptosis. Subversion of innate immune mechanisms by Brucella leads to defective Th1 immune responses and T-cell anergy in chronic brucellosis patients. This review summarizes the cellular immune responses in brucellosis, based on data derived exclusively from human cells or cell lines.
Topics: Antigen-Presenting Cells; Brucella; Brucellosis; Dendritic Cells; Humans; Immunity, Cellular; Macrophages
PubMed: 21034846
DOI: 10.1016/j.micinf.2010.10.015 -
Hormones and Behavior Aug 2012Immune cells and hematopoietic progenitors express estrogen receptors (ER). As ligand-activated transcription factors that modulate chromatin structure, ER regulate... (Review)
Review
Immune cells and hematopoietic progenitors express estrogen receptors (ER). As ligand-activated transcription factors that modulate chromatin structure, ER regulate transcriptional programs that direct the development or functional responses of immune cells. ER-regulated immune responses likely contribute to significant sex biases in infection, autoimmunity and other inflammatory diseases, and changes in immune function during the female hormonal cycle and pregnancy. Here we summarize our own and others' studies showing that ERα signaling regulates the development of dendritic cells (DCs), antigen-presenting cells crucial for initiation of innate and adaptive immunity. During inflammation, elevated GM-CSF directs the development of new DCs from monocytes or other precursors that infiltrate tissues and lymphoid organs, and these de novo populations of inflammatory DCs have critical roles in programming T cell-mediated responses during infection and autoimmunity. Estradiol acting via ERα, but not ERβ, promotes the GM-CSF-mediated inflammatory pathway of DC differentiation, leading to the development of DCs with increased functional capacity. Estradiol/ERα signaling acts directly in GM-CSF-stimulated myeloid progenitors to induce elevated levels of IRF4, a transcription factor that directs a developmental program underlying CD11b⁺ DC differentiation. In contrast, during homeostatic Flt3 Ligand-driven DC development, ERα signaling decreases numbers of myeloid progenitors and differentiated DCs, yet promotes more functionally competent DCs. Thus ERα signaling regulates the response of DC progenitors to the external cytokine environment, thereby altering the strength or integrity of DC developmental pathways. The development of increased numbers of DCs during inflammation will likely increase the magnitude of DC-mediated functional responses including cytokine production, processing and MHC-mediated presentation of antigens, and activation and polarization of T and B lymphocytes; these functions also may be regulated directly by ERα signaling. In sum, via profound effects on DC development and ensuing functional responses, ERα signaling can regulate the quality of the adaptive immune responses and influence the resolution of infection or chronic inflammatory diseases.
Topics: Animals; Cell Differentiation; Dendritic Cells; Immune System; Inflammation; Receptors, Estrogen; Signal Transduction
PubMed: 22561458
DOI: 10.1016/j.yhbeh.2012.04.011 -
Immunotherapy Nov 2010Dendritic cells are the most potent antigen-presenting cells known; owing to their ability to stimulate antigen-specific cytolytic and memory T-cell responses, their use... (Review)
Review
Dendritic cells are the most potent antigen-presenting cells known; owing to their ability to stimulate antigen-specific cytolytic and memory T-cell responses, their use as cancer vaccines is rapidly increasing. While clinical trials provide evidence that dendritic cells vaccines are safe and elicit immunological responses in most patients, few complete tumor remissions have been reported and further technological advances are required. An effective dendritic cell vaccine must possess and maintain several characteristics: it must migrate to lymph nodes, have a mature, Th1-polarizing phenotype expressed stably after infusion and present antigen for sufficient time to produce a T-cell response capable of eliminating a tumor. While dendritic cells are readily matured ex vivo, their phenotype and fate after infusion are rarely evaluable; therefore, strategies to ensure that dendritic cells access lymphoid tissues and retain an immunostimulatory phenotype are required. In order to best exploit dendritic cells as vaccines, they may require genetic modification and combination with other strategies including adoptive T-cell transfer, inhibition of regulatory T cells or modulation of inflammatory pathways.
Topics: Animals; Antigen-Presenting Cells; Antigens, Neoplasm; Cancer Vaccines; Clinical Trials as Topic; Dendritic Cells; Humans; Mice; Neoplasms; T-Lymphocytes; Treatment Outcome
PubMed: 21091116
DOI: 10.2217/imt.10.56 -
Respiratory Research Oct 2015Dendritic cells (DCs) as professional antigen presenting cells (APCs) play a critical role in the regulation of host immune responses. DCs evolve from immature,...
BACKGROUND
Dendritic cells (DCs) as professional antigen presenting cells (APCs) play a critical role in the regulation of host immune responses. DCs evolve from immature, antigen-capturing cells, to mature antigen-presenting cells. The relative contribution of DCs to cigarette smoke-induced inflammation is not well documented. In the current study, we investigated a modulatory effect of cigarette smoke extract (CSE) on differentiation, maturation and function of DCs.
METHODS
Primary murine DCs were grown from bone marrow cells with GM-CSF. Development of DC was analyzed by expression of CD11c, MHCII, CD86, CD40 and CD83 using flow cytometry. Murine DC's and human L428 cells were co-cultured with CSE for various periods of time. Functional activity was analyzed by measuring FITC-dextran uptake, cytokine production and the ability to stimulate T cell activation in a mixed lymphocyte reaction.
RESULTS
Our results show that short-term CSE stimulation (~24 h) influence the maturation status of newly differentiated and immature DCs towards more mature cells as revealed by upregulation of MHCII, CD83, CD86, CD40, reduction in antigen up-take capacity and enhanced secretion of pro-inflammatory (IL-12, IL-6 and TNF-α) cytokines. Interestingly, long-term CSE exposure, time- and concentration-dependently, suppressed the development of functional DCs. This suppression was demonstrated by a decline in CD11c/MHCII, CD83, CD86 and CD40 expression, the production of cytokines and ability to stimulate T lymphocytes. Moreover, CSE significantly suppressed the endocytosis function of mouse DCs which was not due to diminished DC viability. Similar to mouse DCs, long-term co-culturing of the human L428 DC cell line with CSE time-dependently suppressed the expression of CD54.
CONCLUSIONS
The present study provides evidence that CSE modulates DC-mediated immune responses via affecting both the function and maturation of DCs. The suppressive effects of cigarette smoke on DC function might lead to impaired immune responses to various infections.
Topics: Biomarkers; Cell Differentiation; Cell Line, Tumor; Coculture Techniques; Cytokines; Dendritic Cells; Dose-Response Relationship, Drug; Humans; Lymphocyte Activation; Phenotype; Smoke; Smoking; T-Lymphocytes; Time Factors
PubMed: 26498483
DOI: 10.1186/s12931-015-0291-6