scholarly journals The Role of Dendritic Cells in Tissue-Specific Autoimmunity

2014 ◽  
Vol 2014 ◽  
pp. 1-17 ◽  
Author(s):  
Jacques Mbongue ◽  
Dequina Nicholas ◽  
Anthony Firek ◽  
William Langridge
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Clinical Assessment ◽  
Tissue Specific ◽  
Cell Functions ◽  
Research Areas ◽  
Systemic Autoimmunity ◽  
Dendritic Cell Subsets ◽  
Antigen Presenting

In this review, we explore the role of dendritic cell subsets in the development of tissue-specific autoimmune diseases. From the increasing list of dendritic cell subclasses, it is becoming clear that we are only at the beginning of understanding the role of these antigen presenting cells in mediating autoimmunity. Emerging research areas for the study of dendritic cell involvement in the onset and inhibition of tissue-specific autoimmunity are presented. Further, we compare tissue specific to systemic autoimmunity to demonstrate how development of dendritic cell-based therapies may be broadly applicable to both classes of autoimmunity. Continued development of these research areas will lead us closer to clinical assessment of novel immunosuppressive therapy for the reversal and prevention of tissue-specific autoimmunity. Through description of dendritic cell functions in the modulation of tissue-specific autoimmunity, we hope to stimulate a greater appreciation and understanding of the role dendritic cells play in the development and treatment of autoimmunity.

scholarly journals Regulation of the Migration of Distinct Dendritic Cell Subsets

2021 ◽  
Vol 9 ◽  
Author(s):  
Meng Feng ◽  
Shuping Zhou ◽  
Yong Yu ◽  
Qinghong Su ◽  
Xiaofan Li ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Immune Responses ◽  
The Body ◽  
Inflammatory Factors ◽  
Pathogenic Microorganisms ◽  
Migration Patterns ◽  
Dendritic Cell Subsets ◽  
And Migration ◽  
Antigen Presenting

Dendritic cells (DCs), a class of antigen-presenting cells, are widely present in tissues and apparatuses of the body, and their ability to migrate is key for the initiation of immune activation and tolerogenic immune responses. The importance of DCs migration for their differentiation, phenotypic states, and immunologic functions has attracted widespread attention. In this review, we discussed and compared the chemokines, membrane molecules, and migration patterns of conventional DCs, plasmocytoid DCs, and recently proposed DC subgroups. We also review the promoters and inhibitors that affect DCs migration, including the hypoxia microenvironment, tumor microenvironment, inflammatory factors, and pathogenic microorganisms. Further understanding of the migration mechanisms and regulatory factors of DC subgroups provides new insights for the treatment of diseases, such as infection, tumors, and vaccine preparation.

scholarly journals Small Particles, Big Effects: The Interplay Between Exosomes and Dendritic Cells in Antitumor Immunity and Immunotherapy

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1648 ◽  
Author(s):  
Bruno Deltreggia Benites ◽  
Marisa Claudia Alvarez ◽  
Sara Teresinha Olalla Saad
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Myeloid Leukemia ◽  
Antitumor Immunity ◽  
Small Particles ◽  
Cell Functions ◽  
Tumor Exosomes ◽  
Tumor Types ◽  
Antigen Presenting ◽  
Acute Myeloid

Dendritic cells play a fundamental role in the antitumor immunity cycle, and the loss of their antigen-presenting function is a recognized mechanism of tumor evasion. We have recently demonstrated the effect of exosomes extracted from serum of patients with acute myeloid leukemia as important inducers of dendritic cell immunotolerance, and several other works have recently demonstrated the effects of these nanoparticles on immunity to other tumor types as well. The aim of this review was to highlight the recent findings on the effects of tumor exosomes on dendritic cell functions, the mechanisms by which they can lead to tumor evasion, and their manipulation as a possible strategy in cancer treatment.

scholarly journals Functional Role of Dendritic Cell Subsets in Cancer Progression and Clinical Implications

2020 ◽  
Vol 21 (11) ◽  
pp. 3930
Author(s):  
Annalisa Del Prete ◽  
Francesca Sozio ◽  
Ilaria Barbazza ◽  
Valentina Salvi ◽  
Laura Tiberio ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
Cancer Progression ◽  
Cell Response ◽  
Functional Role ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
Dendritic Cell Subsets

Dendritic cells (DCs) constitute a complex network of cell subsets with common functions but also with many divergent aspects. All dendritic cell subsets share the ability to prime T cell response and to undergo a complex trafficking program related to their stage of maturation and function. For these reasons, dendritic cells are implicated in a large variety of both protective and detrimental immune responses, including a crucial role in promoting anti-tumor responses. Although cDC1s are the most potent subset in tumor antigen cross-presentation, they are not sufficient to induce full-strength anti-tumor cytotoxic T cell response and need close interaction and cooperativity with the other dendritic cell subsets, namely cDC2s and pDCs. This review will take into consideration different aspects of DC biology, including the functional role of dendritic cell subsets in both fostering and suppressing tumor growth, the mechanisms underlying their recruitment into the tumor microenvironment, as well as the prognostic value and the potentiality of dendritic cell therapeutic targeting. Understanding the specificity of dendritic cell subsets will allow to gain insights on role of these cells in pathological conditions and to design new selective promising therapeutic approaches.

scholarly journals PATHOPHYSIOLOGY OF DENDRITIC CELLS IN CANCER

2016 ◽  
Vol 15 (4) ◽  
pp. 25-33
Author(s):  
A. A. Keskinov ◽  
M. R. Shurin ◽  
V. M. Bukhman ◽  
Z. S. Shprakh
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
Tumor Antigens ◽  
Cancer Surveillance ◽  
Adoptive Therapy ◽  
Cell Functions ◽  
Cell Based Therapy ◽  
Antigen Presenting ◽  
The Impact

Immune system plays a crucial role in tumor growth process. It exerts cancer surveillance function via innate and adaptive immune mechanisms, nonetheless tumor may exploit various immune cells to escape specific immune response. Dendritic cells are the primary antigen presenting cells, which mediate immune response against cancer cells. Dendritic cells are capable of processing and presenting tumor antigens to T cells, which results in tumor-specific T cell- mediated response. However, adoptive therapy with dendritic cells demonstrates poor clinical outcomes. Among a variety of factors, the impact of tumor microenvironment on dendritic cells may be the primary one. Therefore, tumor-derived factors, which lead to dendritic cells malfunction, may be the key target for improving dendritic cell - based therapy. Meanwhile, recovery of dendritic cell functions in cancer patients remains one of primary aims for cancer immunotherapy. This review outlines main types of tumor-induced dendritic cells dysfunctions in cancer.

scholarly journals Dendritic Cells at the Oral Mucosal Interface

2006 ◽  
Vol 85 (8) ◽  
pp. 678-689 ◽  
Author(s):  
C.W. Cutler ◽  
R. Jotwani
Keyword(s):  
Dendritic Cells ◽  
Immune System ◽  
Dendritic Cell ◽  
Oral Mucosa ◽  
The Body ◽  
Tumor Origin ◽  
Mucosal Lining ◽  
Dendritic Cell Subsets ◽  
Oral Microbes

The mucosal lining of the respiratory and digestive systems contains the largest and most complex immune system in the body, but surprisingly little is known of the immune system that serves the oral mucosa. This review focuses on dendritic cells, particularly powerful arbiters of immunity, in response to antigens of microbial or tumor origin, but also of tolerance to self-antigens and commensal microbes. Although first discovered in 1868, the epidermal dendritic Langerhans cells remained enigmatic for over a century, until they were identified as the most peripheral outpost of the immune system. Investigators’ ability to isolate, enrich, and culture dendritic cells has led to an explosion in the field. Presented herein is a review of dendritic cell history, ontogeny, function, and phenotype, and the role of different dendritic cell subsets in the oral mucosa and its diseases. Particular emphasis is placed on the mechanisms of recognition and capture of microbes by dendritic cells. Also emphasized is how dendritic cells may regulate immunity/tolerance in response to oral microbes.

Expression of Tyk2 in dendritic cells is required for IL-12, IL-23, and IFN-γ production and the induction of Th1 cell differentiation

Blood ◽  
2007 ◽  
Vol 110 (2) ◽  
pp. 553-560 ◽  
Author(s):  
Naoki Tokumasa ◽  
Akira Suto ◽  
Shin-ichiro Kagami ◽  
Shunsuke Furuta ◽  
Koichi Hirose ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Cell Differentiation ◽  
Cpg Odn ◽  
T Helper ◽  
Dc Functions ◽  
Th1 Cell ◽  
Th2 Cell ◽  
Ifn Γ ◽  
Antigen Presenting

Abstract It is well documented that dendritic cells (DCs), representative antigen-presenting cells, are important sources of Th1-promoting cytokines and are actively involved in the regulation of T-helper–cell differentiation. However, the intracellular event that regulates this process is still largely unknown. In this study, we examined the role of Tyk2, a JAK kinase that is involved in the signaling pathway under IL-12 and IL-23, in DC functions. While the differentiation and maturation of DCs was normal in Tyk2-deficient (Tyk2−/−) mice, IL-12–induced Stat4 phosphorylation was diminished in Tyk2−/− DCs. IL-12–induced IFN-γ production was also significantly diminished in Tyk2−/− DCs to levels similar to those in Stat4−/− DCs. Interestingly, Tyk2−/− DCs were defective in IL-12 and IL-23 production upon stimulation with CpG ODN. Furthermore, Tyk2−/− DCs were impaired in their ability to induce Th1-cell differentiation but not Th2-cell differentiation. Taken together, these results indicate that the expression of Tyk2 in DCs is crucial for the production of Th1-promoting cytokines such as IL-12 and IFN-γ from DCs and thereby for the induction of antigen-specific Th1-cell differentiation.

scholarly journals Small amounts of superantigen, when presented on dendritic cells, are sufficient to initiate T cell responses.

1993 ◽  
Vol 178 (2) ◽  
pp. 633-642 ◽  
Author(s):  
N Bhardwaj ◽  
J W Young ◽  
A J Nisanian ◽  
J Baggers ◽  
R M Steinman
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
Mhc Class Ii ◽  
Cell Receptor ◽  
Class Ii ◽  
Cell Mediated Immunity ◽  
Quiescent T Cells ◽  
Antigen Presenting

Dendritic cells are potent antigen-presenting cells for several primary immune responses and therefore provide an opportunity for evaluating the amounts of cell-associated antigens that are required for inducing T cell-mediated immunity. Because dendritic cells express very high levels of major histocompatibility complex (MHC) class II products, it has been assumed that high levels of ligands bound to MHC products ("signal one") are needed to stimulate quiescent T cells. Here we describe quantitative aspects underlying the stimulation of human blood T cells by a bacterial superantigen, staphylococcal enterotoxin A (SEA). The advantages of superantigens for quantitative studies of signal one are that these ligands: (a) engage MHC class II and the T cell receptor but do not require processing; (b) are efficiently presented to large numbers of quiescent T cells; and (c) can be pulsed onto dendritic cells before their application to T cells. Thus one can relate amounts of dendritic cell-associated SEA to subsequent lymphocyte stimulation. Using radioiodinated SEA, we noted that dendritic cells can bind 30-200 times more superantigen than B cells and monocytes. Nevertheless, this high SEA binding does not underlie the strong potency of dendritic cells to present antigen to T cells. Dendritic cells can sensitize quiescent T cells, isolated using monoclonals to appropriate CD45R epitopes, after a pulse of SEA that occupies a maximum of 0.1% of surface MHC class II molecules. This corresponds to an average of 2,000 molecules per dendritic cell. At these low doses of bound SEA, monoclonal antibodies to CD3, CD4, and CD28 almost completely block T cell proliferation. In addition to suggesting new roles for MHC class II on dendritic cells, especially the capture and retention of ligands at low external concentrations, the data reveal that primary T cells can generate a response to exceptionally low levels of signal one as long as these are delivered on dendritic cells.

scholarly journals Dendritic cells mediate the induction of polyfunctional human IL17-producing cells (Th17-1 cells) enriched in the bone marrow of patients with myeloma

Blood ◽  
2008 ◽  
Vol 112 (7) ◽  
pp. 2878-2885 ◽  
Author(s):  
Kavita M. Dhodapkar ◽  
Scott Barbuto ◽  
Phillip Matthews ◽  
Anjli Kukreja ◽  
Amitabha Mazumder ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Th17 Cells ◽  
T Helper ◽  
Tumor Bed ◽  
Distinct Lineage ◽  
Human Dendritic Cells ◽  
Antigen Presenting ◽  
Dc Maturation

Abstract IL17-producing (Th17) cells are a distinct lineage of T helper cells that regulate immunity and inflammation. The role of antigen-presenting cells in the induction of Th17 cells in humans remains to be fully defined. Here, we show that human dendritic cells (DCs) are efficient inducers of Th17 cells in culture, including antigen-specific Th17 cells. Although most freshly isolated circulating human Th17 cells secrete IL17 alone or with IL2, those induced by DCs are polyfunctional and coexpress IL17 and IFNγ (Th17-1 cells). The capacity of DCs to expand Th17-1 cells is enhanced upon DC maturation, and mature DCs are superior to monocytes for the expansion of autologous Th17 cells. In myeloma, where tumors are infiltrated by DCs, Th17 cells are enriched in the bone marrow relative to circulation. Bone marrow from patients with myeloma contains a higher proportion of Th17-1 cells compared with the marrow in preneoplastic gammopathy (monoclonal gammopathy of undetermined significance [MGUS]). Uptake of apoptotic but not necrotic myeloma tumor cells by DCs leads to enhanced induction of Th17-1 cells. These data demonstrate the capacity of DCs to induce expansion of polyfunctional IL17-producing T cells in humans, and suggest a role for DCs in the enrichment of Th17-1 cells in the tumor bed.

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