Migration of dendritic cells across blood and lymphatic endothelial barriers

SummaryDendritic cells (DC) are professional antigen presenting cells which playa pivotal role in the activation of adaptive immunity. Tissue invasion by pathogens induces the recruitment of blood DC to the site of infection and contributes to their subsequent migration to secondary lymphoid organs. This complex process relies on the expression and regulation of receptors for chemotactic factors on the surface of migrating DC and on the activation of adhesion molecules which allow DC to properly interact with both blood and lymphatic vessels. In the absence of correct tissue localization, DC fail to promote proper immune responses. Therefore, the interaction of DC with endothelial cells represents a fundamental step for DC biology.

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Similar antigen cross-presentation capacity and phagocytic functions in all freshly isolated human lymphoid organ–resident dendritic cells

Journal of Experimental Medicine ◽

10.1084/jem.20121103 ◽

2013 ◽

Vol 210 (5) ◽

pp. 1035-1047 ◽

Cited By ~ 163

Author(s):

Elodie Segura ◽

Mélanie Durand ◽

Sebastian Amigorena

Keyword(s):

Dendritic Cells ◽

Immune Responses ◽

Lymphoid Organ ◽

Lymphoid Organs ◽

Endocytic Pathway ◽

Soluble Antigen ◽

Cross Presentation ◽

Antigen Presenting ◽

Secondary Lymphoid Organs

Dendritic cells (DCs) represent a heterogeneous population of antigen-presenting cells that initiate and orient immune responses in secondary lymphoid organs. In mice, lymphoid organ–resident CD8+ DCs are specialized at cross-presentation and have developed specific adaptations of their endocytic pathway (high pH, low degradation, and high export to the cytosol). In humans, blood BDCA3+ DCs were recently shown to be the homologues of mouse CD8+ DCs. They were also proposed to cross-present antigens more efficiently than other blood DC subsets after in vitro activation, suggesting that in humans cross-presentation is restricted to certain DC subsets. The DCs that cross-present antigen physiologically, however, are the ones present in lymphoid organs. Here, we show that freshly isolated tonsil-resident BDCA1+ DCs, BDCA3+ DCs, and pDCs all cross-present soluble antigen efficiently, as compared to macrophages, in the absence of activation. In addition, BDCA1+ and BDCA3+ DCs display similar phagosomal pH and similar production of reactive oxygen species in their phagosomes. All three DC subsets, in contrast to macrophages, also efficiently export internalized proteins to the cytosol. We conclude that all freshly isolated lymphoid organ–resident human DCs, but not macrophages, display high intrinsic cross-presentation capacity.

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Antigen-Specific Polyclonal Cytotoxic T Lymphocytes Induced by Fusions of Dendritic Cells and Tumor Cells

Journal of Biomedicine and Biotechnology ◽

10.1155/2010/752381 ◽

2010 ◽

Vol 2010 ◽

pp. 1-12 ◽

Cited By ~ 6

Author(s):

Shigeo Koido ◽

Sadamu Homma ◽

Eiichi Hara ◽

Yoshihisa Namiki ◽

Toshifumi Ohkusa ◽

...

Keyword(s):

Dendritic Cells ◽

T Lymphocytes ◽

Immune Responses ◽

Tumor Cells ◽

Cytotoxic T Lymphocytes ◽

Alternative Approach ◽

Antigen Presenting ◽

Ctl Induction ◽

Secondary Lymphoid Organs ◽

Powerful Strategy

The aim of cancer vaccines is induction of tumor-specific cytotoxic T lymphocytes (CTLs) that can reduce the tumor mass. Dendritic cells (DCs) are potent antigen-presenting cells and play a central role in the initiation and regulation of primary immune responses. Thus, DCs-based vaccination represents a potentially powerful strategy for induction of antigen-specific CTLs. Fusions of DCs and whole tumor cells represent an alternative approach to deliver, process, and subsequently present a broad spectrum of antigens, including those known and unidentified, in the context of costimulatory molecules. Once DCs/tumor fusions have been infused back into patient, they migrate to secondary lymphoid organs, where the generation of antigen-specific polyclonal CTL responses occurs. We will discuss perspectives for future development of DCs/tumor fusions for CTL induction.

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Functional domains of HSP70 stimulate generation of cytokines and chemokines, maturation of dendritic cells and adjuvanticity

Biochemical Society Transactions ◽

10.1042/bst0320629 ◽

2004 ◽

Vol 32 (4) ◽

pp. 629-632 ◽

Cited By ~ 65

Author(s):

T. Lehner ◽

Y. Wang ◽

T. Whittall ◽

E. McGowan ◽

C.G. Kelly ◽

...

Keyword(s):

Amino Acids ◽

Dendritic Cells ◽

Immune Responses ◽

Cd40 Ligand ◽

Interleukin 12 ◽

Cytokines And Chemokines ◽

Cc Chemokines ◽

Factor Α ◽

Antigen Presenting ◽

Necrosis Factor

Microbial HSP70 (heat-shock protein 70) consists of three functionally distinct domains: an N-terminal 44 kDa ATPase portion (amino acids 1–358), followed by an 18 kDa peptide-binding domain (amino acids 359–494) and a C-terminal 10 kDa fragment (amino acids 495–609). Immunological functions of these three different domains in stimulating monocytes and dendritic cells have not been fully defined. However, the C-terminal portion (amino acids 359–610) stimulates the production of CC chemokines, IL-12 (interleukin-12), TNFα(tumour necrosis factor α), NO and maturation of dendritic cells and also functions as an adjuvant in the induction of immune responses. In contrast, the ATPase domain of microbial HSP70 mostly lacks these functions. Since the receptor for HSP70 is CD40, which with its CD40 ligand constitutes a major co-stimulatory pathway in the interaction between antigen-presenting cells and T-cells, HSP70 may function as an alternative ligand to CD40L. HSP70–CD40 interaction has been demonstrated in non-human primates to play a role in HIV infection, in protection against Mycobacterium tuberculosis and in conversion of tolerance to immunity.

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Regulation of the Migration of Distinct Dendritic Cell Subsets

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.635221 ◽

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.

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Evaluation of Feline Monocyte-Derived Dendritic Cells Loaded with Internally Inactivated Virus as a Vaccine against Feline Immunodeficiency Virus

Clinical and Vaccine Immunology ◽

10.1128/cvi.00421-07 ◽

2008 ◽

Vol 15 (3) ◽

pp. 452-459 ◽

Cited By ~ 4

Author(s):

Giulia Freer ◽

Donatella Matteucci ◽

Paola Mazzetti ◽

Francesca Tarabella ◽

Valentina Catalucci ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Immune Responses ◽

Immune Functions ◽

Peripheral Blood Mononuclear ◽

Challenge Virus ◽

Homologous Virus ◽

Antibody Titers ◽

Cellular Immune ◽

Antigen Presenting

ABSTRACT Dendritic cells are the only antigen-presenting cells that can present exogenous antigens to both helper and cytolytic T cells and prime Th1-type or Th2-type cellular immune responses. Given their unique immune functions, dendritic cells are considered attractive “live adjuvants” for vaccination and immunotherapy against cancer and infectious diseases. The present study was carried out to assess whether the reinjection of autologous monocyte-derived dendritic cells loaded with an aldithriol-2-inactivated primary isolate of feline immune deficiency virus (FIV) was able to elicit protective immune responses against the homologous virus in naive cats. Vaccine efficacy was assessed by monitoring immune responses and, finally, by challenge with the homologous virus of vaccinated, mock-vaccinated, and healthy cats. The outcome of challenge was followed by measuring cellular and antibody responses and viral and proviral loads and quantitating FIV by isolation and a count of CD4+/CD8+ T cells in blood. Vaccinated animals exhibited clearly evident FIV-specific peripheral blood mononuclear cell proliferation and antibody titers in response to immunization; however, they became infected with the challenge virus at rates comparable to those of control animals.

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Manipulating dendritic cell biology for the active immunotherapy of cancer

Blood ◽

10.1182/blood-2003-12-4392 ◽

2004 ◽

Vol 104 (8) ◽

pp. 2235-2246 ◽

Cited By ~ 233

Author(s):

David W. O'Neill ◽

Sylvia Adams ◽

Nina Bhardwaj

Keyword(s):

Dendritic Cells ◽

Immune Responses ◽

Cell Biology ◽

Active Immunotherapy ◽

Transplantation Tolerance ◽

Chronic Infections ◽

Immunotherapy Of Cancer ◽

Antigen Presenting ◽

And Control ◽

New Strategies

Abstract Dendritic cells (DCs) are specialized antigen-presenting cells (APCs) that have an unequaled capacity to initiate primary immune responses, including tolerogenic responses. Because of the importance of DCs in the induction and control of immunity, an understanding of their biology is central to the development of potent immunotherapies for cancer, chronic infections, autoimmune disease, and induction of transplantation tolerance. This review discusses recent advances in DC research and the application of this knowledge toward new strategies for the clinical manipulation of DCs for cancer immunotherapy.

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Single-cell mapping reveals new markers and functions of lymphatic endothelial cells in lymph nodes

10.1101/2020.01.09.900241 ◽

2020 ◽

Cited By ~ 1

Author(s):

Noriki Fujimoto ◽

Yuliang He ◽

Marco D’Addio ◽

Carlotta Tacconi ◽

Michael Detmar ◽

...

Keyword(s):

Endothelial Cells ◽

Immune Responses ◽

Lymph Nodes ◽

Single Cell ◽

Cancer Metastasis ◽

Lymphatic Vessels ◽

Peripheral Tolerance ◽

Lymphatic Endothelial Cells ◽

Subcapsular Sinus ◽

Lymphocyte Egress

ABSTRACTLymph nodes (LNs) are highly organized secondary lymphoid organs that mediate adaptive immune responses to antigens delivered via afferent lymphatic vessels. Lymphatic endothelial cells (LECs) line intranodal lymphatic sinuses and organize lymph and antigen distribution. LECs also directly regulate T cells, mediating peripheral tolerance to self-antigens, and play a major role in many diseases including cancer metastasis. However, little is known about the phenotypic and functional heterogeneity of LN LECs. Using single-cell RNA sequencing, we comprehensively defined the transcriptome of LECs in murine skin-draining LNs, and identified new markers and functions of distinct LEC subpopulations. We found that LECs residing in the subcapsular sinus have an unanticipated function in scavenging of modified LDL and also identified a specific cortical LEC subtype implicated in rapid lymphocyte egress from LNs. Our data provide new insights into the diversity of LECs in murine lymph nodes and a rich resource for future studies into the regulation of immune responses by lymph node LECs.

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Enpp2 Expression by Dendritic Cells Is a Key Regulator in Migration

Biomedicines ◽

10.3390/biomedicines9111727 ◽

2021 ◽

Vol 9 (11) ◽

pp. 1727

Author(s):

Jun-Ho Lee ◽

So-Yeon Choi ◽

Soo-Yeoun Park ◽

Nam-Chul Jung ◽

Kyung-Eun Noh ◽

...

Keyword(s):

Dendritic Cells ◽

Lymph Nodes ◽

Cancer Vaccines ◽

Biological Effects ◽

Migratory Capacity ◽

Migration Capacity ◽

Antigen Presenting ◽

Si Rna ◽

Secondary Lymphoid Organs

Enpp2 is an enzyme that catalyzes the conversion of lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), which exhibits a wide variety of biological functions. Here, we examined the biological effects of Enpp2 on dendritic cells (DCs), which are specialized antigen-presenting cells (APCs) characterized by their ability to migrate into secondary lymphoid organs and activate naïve T-cells. DCs were generated from bone marrow progenitors obtained from C57BL/6 mice. Enpp2 levels in DCs were regulated using small interfering (si)RNA or recombinant Enpp2. Expression of Enpp2 in LPS-stimulated mature (m)DCs was high, however, knocking down Enpp2 inhibited mDC function. In addition, the migratory capacity of mDCs increased after treatment with rmEnpp2; this phenomenon was mediated via the RhoA-mediated signaling pathway. Enpp2-treated mDCs showed a markedly increased capacity to migrate to lymph nodes in vivo. These findings strongly suggest that Enpp2 is necessary for mDC migration capacity, thereby increasing our understanding of DC biology. We postulate that regulating Enpp2 improves DC migration to lymph nodes, thus improving the effectiveness of cancer vaccines based on DC.

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Dendritic Cells: Critical Regulators of Allergic Asthma

International Journal of Molecular Sciences ◽

10.3390/ijms21217930 ◽

2020 ◽

Vol 21 (21) ◽

pp. 7930 ◽

Cited By ~ 1

Author(s):

Ioannis Morianos ◽

Maria Semitekolou

Keyword(s):

Dendritic Cells ◽

Immune Responses ◽

Airway Inflammation ◽

Allergic Asthma ◽

Allergic Airway Inflammation ◽

Chronic Inflammatory Disease ◽

Antigen Presenting ◽

Airborne Allergens

Allergic asthma is a chronic inflammatory disease of the airways characterized by airway hyperresponsiveness (AHR), chronic airway inflammation, and excessive T helper (Th) type 2 immune responses against harmless airborne allergens. Dendritic cells (DCs) represent the most potent antigen-presenting cells of the immune system that act as a bridge between innate and adaptive immunity. Pertinent to allergic asthma, distinct DC subsets are known to play a central role in initiating and maintaining allergen driven Th2 immune responses in the airways. Nevertheless, seminal studies have demonstrated that DCs can also restrain excessive asthmatic responses and thus contribute to the resolution of allergic airway inflammation and the maintenance of pulmonary tolerance. Notably, the transfer of tolerogenic DCs in vivo suppresses Th2 allergic responses and protects or even reverses established allergic airway inflammation. Thus, the identification of novel DC subsets that possess immunoregulatory properties and can efficiently control aberrant asthmatic responses is critical for the re-establishment of tolerance and the amelioration of the asthmatic disease phenotype.

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Antibody Response after Vaccination with Antigen-Pulsed Dendritic Cells

The International Journal of Biological Markers ◽

10.1177/172460080401900306 ◽

2004 ◽

Vol 19 (3) ◽

pp. 213-220

Author(s):

F. Battaini ◽

D. Besusso ◽

L. Sfondrini ◽

A. Rossini ◽

D. Morelli ◽

...

Keyword(s):

Dendritic Cells ◽

Immune System ◽

Immune Responses ◽

Antibody Response ◽

Cancer Patients ◽

Antibody Production ◽

Tumor Antigens ◽

Antigen Uptake ◽

Antigen Presenting

Dendritic cells (DCs) are the most potent antigen-presenting cells of the immune system capable of initiating immune responses to antigens. It is also well documented that cancer patients often experience anergy against tumor antigens. In this study we selected the best protocol for inducing the production of antibodies against the HER2 oncoprotein using DCs to overcome anergy. Murine DCs were pulsed in vitro, using different protocols, with recombinant HER2 fused to a human Fc (in order to improve DC antigen uptake) and were used to vaccinate mice. The obtained results indicate that antigen-pulsed DCs can induce an antibody response and that adding CpG after antigen pulsing greatly increases anti-HER2 antibody production.

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