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migratory Dendritic cells

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https://www.readbyqxmd.com/read/27890914/dendritic-cell-migration-in-health-and-disease
#1
Tim Worbs, Swantje I Hammerschmidt, Reinhold Förster
Dendritic cells (DCs) are potent and versatile antigen-presenting cells, and their ability to migrate is key for the initiation of protective pro-inflammatory as well as tolerogenic immune responses. Recent comprehensive studies have highlighted the importance of DC migration in the maintenance of immune surveillance and tissue homeostasis, and also in the pathogenesis of a range of diseases. In this Review, we summarize the anatomical, cellular and molecular factors that regulate the migration of different DC subsets in health and disease...
November 28, 2016: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/27852743/immunogenic-dendritic-cell-generation-from-pluripotent-stem-cells-by-ectopic-expression-of-runx3
#2
Erika Takacs, Pal Boto, Emilia Simo, Tamas I Csuth, Bianka M Toth, Hadas Raveh-Amit, Attila Pap, Elek G Kovács, Julianna Kobolak, Szilvia Benkö, Andras Dinnyes, Istvan Szatmari
Application of dendritic cells (DCs) to prime responses to tumor Ags provides a promising approach to immunotherapy. However, only a limited number of DCs can be manufactured from adult precursors. In contrast, pluripotent embryonic stem (ES) cells represent an inexhaustible source for DC production, although it remains a major challenge to steer directional differentiation because ES cell-derived cells are typically immature with impaired functional capacity. Consistent with this notion, we found that mouse ES cell-derived DCs (ES-DCs) represented less mature cells compared with bone marrow-derived DCs...
November 16, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27826300/treatment-with-dexamethasone-and-monophosphoryl-lipid-a-removes-disease-associated-transcriptional-signatures-in-monocyte-derived-dendritic-cells-from-rheumatoid-arthritis-patients-and-confers-tolerogenic-features
#3
Paulina A García-González, Katina Schinnerling, Alejandro Sepúlveda-Gutiérrez, Jaxaira Maggi, Lorena Hoyos, Rodrigo A Morales, Ahmed M Mehdi, Hendrik J Nel, Lilian Soto, Bárbara Pesce, María Carmen Molina, Miguel Cuchacovich, Milton L Larrondo, Óscar Neira, Diego Francisco Catalán, Catharien M Hilkens, Ranjeny Thomas, Ricardo A Verdugo, Juan C Aguillón
Tolerogenic dendritic cells (TolDCs) are promising tools for therapy of autoimmune diseases, such as rheumatoid arthritis (RA). Here, we characterize monocyte-derived TolDCs from RA patients modulated with dexamethasone and activated with monophosphoryl lipid A (MPLA), referred to as MPLA-tDCs, in terms of gene expression, phenotype, cytokine profile, migratory properties, and T cell-stimulatory capacity in order to explore their suitability for cellular therapy. MPLA-tDCs derived from RA patients displayed an anti-inflammatory profile with reduced expression of co-stimulatory molecules and high IL-10/IL-12 ratio, but were capable of migrating toward the lymphoid chemokines CXCL12 and CCL19...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27820700/the-transcription-factor-nr4a3-controls-cd103-dendritic-cell-migration
#4
Kiwon Park, Zbigniew Mikulski, Goo-Young Seo, Aleksander Y Andreyev, Paola Marcovecchio, Amy Blatchley, Mitchell Kronenberg, Catherine C Hedrick
The transcription factor NR4A3 (also known as NOR-1) is a member of the Nr4a family of nuclear receptors and is expressed in myeloid and lymphoid cells. Here, we have shown that Nr4a3 is essential for the migration of CD103+ dendritic cells (DCs) to lymph nodes (LNs). Nr4a3-deficient mice had very few CD103+ migratory DCs (mDCs) present in LNs, and mixed-chimera studies revealed that this migratory defect was cell intrinsic. We further found that CD103+ DCs from Nr4a3-deficient mice displayed a marked loss of surface expression of the chemokine CCR7...
December 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27819270/a-microfluidic-device-for-measuring-cell-migration-towards-substrate-bound-and-soluble-chemokine-gradients
#5
Jan Schwarz, Veronika Bierbaum, Jack Merrin, Tino Frank, Robert Hauschild, Tobias Bollenbach, Savaş Tay, Michael Sixt, Matthias Mehling
Cellular locomotion is a central hallmark of eukaryotic life. It is governed by cell-extrinsic molecular factors, which can either emerge in the soluble phase or as immobilized, often adhesive ligands. To encode for direction, every cue must be present as a spatial or temporal gradient. Here, we developed a microfluidic chamber that allows measurement of cell migration in combined response to surface immobilized and soluble molecular gradients. As a proof of principle we study the response of dendritic cells to their major guidance cues, chemokines...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27808089/splenic-differentiation-and-emergence-of-ccr5-cxcl9-cxcl10-monocyte-derived-dendritic-cells-in-the-brain-during-cerebral-malaria
#6
Isabella C Hirako, Marco A Ataide, Lucas Faustino, Patricia A Assis, Elizabeth W Sorensen, Hisashi Ueta, Natalia M Araújo, Gustavo B Menezes, Andrew D Luster, Ricardo T Gazzinelli
Dendritic cells have an important role in immune surveillance. After being exposed to microbial components, they migrate to secondary lymphoid organs and activate T lymphocytes. Here we show that during mouse malaria, splenic inflammatory monocytes differentiate into monocyte-derived dendritic cells (MO-DCs), which are CD11b(+)F4/80(+)CD11c(+)MHCII(high)DC-SIGN(high)Ly6c(+) and express high levels of CCR5, CXCL9 and CXCL10 (CCR5(+)CXCL9/10(+) MO-DCs). We propose that malaria-induced splenic MO-DCs take a reverse migratory route...
November 3, 2016: Nature Communications
https://www.readbyqxmd.com/read/27768071/a-cfse-based-assay-to-study-the-migration-of-murine-skin-dendritic-cells-into-draining-lymph-nodes-during-infection-with-mycobacterium-bovis-bacille-calmette-gu%C3%A3-rin
#7
Vishnu Priya Bollampalli, Susanne Nylén, Antonio Gigliotti Rothfuchs
Dendritic cells (DCs) are important for initiating immune responses, in part through their ability to acquire and shuttle antigen to the draining lymph node (DLN). The mobilization of DCs to the DLN is complex and remains to be fully elucidated during infection. Herein described is the use of an innovative, simple assay that relies on the fluorochrome 5- and 6-carboxyfluorescein diacetate succinimidyl ester (CFSE) to track the migration of DCs during footpad infection with Mycobacterium bovis Bacille Calmette-Guérin (BCG) in C57BL/6 mice...
October 9, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27683749/il-10-modulated-human-dendritic-cells-for-clinical-use-identification-of-a-stable-and-migratory-subset-with-improved-tolerogenic-activity
#8
Fanny Kryczanowsky, Verena Raker, Edith Graulich, Matthias P Domogalla, Kerstin Steinbrink
Dendritic cells (DCs) are key regulators of protective immune responses and tolerance to (self-)Ags. Therefore, the scientific rationale for the use of tolerogenic DC therapy in the fields of allergies, autoimmunity, and transplantation medicine is strong. In this study, we analyzed the tolerogenic capacity of IL-10-modulated DC (IL-10DC) subpopulations to identify a DC subset that combines potent immunosuppressive activities with valuable immune properties for clinical implementation. IL-10DCs consist of two phenotypically distinct subpopulations: CD83(high)CCR7(+) IL-10DCs and CD83(low)CCR7(-) IL-10DCs...
September 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27670791/the-contributions-of-lung-macrophage-and-monocyte-heterogeneity-to-influenza-pathogenesis
#9
Mubing Duan, Margaret L Hibbs, Weisan Chen
The lung myeloid cell microenvironment comprises airway, alveolar and interstitial macrophages, peripheral blood recruited lung monocytes as well as residential and migratory dendritic cell subsets. Findings from fate mapping, parabiosis, transcriptome and epigenome profiling studies now indicate that tissue macrophage and monocyte subsets possess specialized functions which differentially impact homoeostatic tolerance, pathogen detection and pathogen killing. In the lungs, residential alveolar macrophages are catabolic and immunosuppressive in contrast to the classically pro-inflammatory repertoire of lung monocytes and monocyte-derived dendritic cells recruited during acute inflammation...
October 18, 2016: Immunology and Cell Biology
https://www.readbyqxmd.com/read/27628546/-cancer-immunotherapy-using-human-induced-pluripotent-stem-cell-derived-dendritic-cells-ipsdcs-expressing-carcinoembryonic-antigen
#10
Junya Kitadani, Toshiyasu Ojima, Hiromitsu Iwamoto, Hiroaki Tabata, Mikihito Nakamori, Masaki Nakamura, Masahiro Katsuda, Motoki Miyazawa, Keiji Hayata, Hiroki Yamaue
The difficulty in obtaining a sufficient number of functional dendritic cells(DCs)is a well-known serious problem in DCbased immunotherapy. Therefore, we used induced pluripotent stem cell-derived DCs(iPSDCs). We have reported that mouse iPSDCs are equivalent to BMDCs, in terms of maturation and antigen presentation. In this study, the antitumor immune response of human iPSDCs expressing the carcinoembryonic antigen was examined, to determine its clinical application in gastrointestinal cancer. Human iPS cells were established from healthy human fibroblasts using a Sendai virus vector, and human iPSDCs were differentiated under a feeder-free culture...
September 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/27592607/plasmacytoid-dendritic-cells-induce-tolerance-predominantly-by-cargoing-antigen-to-lymph-nodes
#11
Karan Kohli, Anika Janssen, Reinhold Förster
Plasmacytoid dendritic cells (pDCs) have been shown to induce tolerance to innocuous antigens. Their migratory properties allow them to take up antigens from the periphery and transport them to the draining lymph nodes or to the thymus. However, pDC-T-cell interaction in the primary and secondary lymphoid organs still remains poorly defined. In this study, we show that resting pDCs loaded with exogenous antigen could induce tolerance when transferred intralymphatically into a single lymph node of wild-type C57BL/6 mice...
November 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27574990/the-administration-route-is-decisive-for-the-ability-of-the-vaccine-adjuvant-caf09-to-induce-antigen-specific-cd8-t-cell-responses-the-immunological-consequences-of-the-biodistribution-profile
#12
Signe Tandrup Schmidt, Swapnil Khadke, Karen Smith Korsholm, Yvonne Perrie, Thomas Rades, Peter Andersen, Camilla Foged, Dennis Christensen
A prerequisite for vaccine-mediated induction of CD8(+) T-cell responses is the targeting of dendritic cell (DC) subsets specifically capable of cross-presenting antigen epitopes to CD8(+) T cells. Administration of a number of cationic adjuvants via the intraperitoneal (i.p.) route has been shown to result in strong CD8(+) T-cell responses, whereas immunization via e.g. the intramuscular (i.m.) or subcutaneous (s.c.) routes often stimulate weak CD8(+) T-cell responses. The hypothesis for this is that self-drainage of the adjuvant/antigen to the lymphoid organs, which takes place upon i...
October 10, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27549170/the-lymphatic-immune-response-induced-by-the-adjuvant-as01-a-comparison-of-intramuscular-and-subcutaneous-immunization-routes
#13
Melanie R Neeland, Wei Shi, Catherine Collignon, Nadine Taubenheim, Els N T Meeusen, Arnaud M Didierlaurent, Michael J de Veer
The liposome-based adjuvant AS01 incorporates two immune stimulants, 3-O-desacyl-4'-monophosphoryl lipid A and the saponin QS-21. AS01 is under investigation for use in several vaccines in clinical development. i.m. injection of AS01 enhances immune cell activation and dendritic cell (DC) Ag presentation in the local muscle-draining lymph node. However, cellular and Ag trafficking in the lymphatic vessels that connect an i.m. injection site with the local lymph node has not been investigated. The objectives of this study were: 1) to quantify the in vivo cellular immune response induced by AS01 in an outbred ovine model, 2) to develop a lymphatic cannulation model that directly collects lymphatic fluid draining the muscle, and 3) to investigate the function of immune cells entering and exiting the lymphatic compartments after s...
October 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27543048/medullary-thymic-epithelial-cells-and-cd8%C3%AE-dendritic-cells-coordinately-regulate-central-tolerance-but-cd8%C3%AE-cells-are-dispensable-for-thymic-regulatory-t-cell-production
#14
Olivier Herbin, Anthony J Bonito, Seihwan Jeong, Erica G Weinstein, Adeeb H Rahman, Huabao Xiong, Miriam Merad, Konstantina Alexandropoulos
In the thymus, antigen presenting cells (APCs) namely, medullary thymic epithelial cells (mTECs) and thymic dendritic cells (tDCs) regulate T cell tolerance through elimination of autoreactive T cells and production of thymic T regulatory (tTreg) cells. How the different APCs in the thymus share the burden of tolerazing the emerging T cell repertoire remains unclear. For example, while mutations that inhibit mTEC development or function associate with peripheral autoimmunity, the role of tDCs in organ-specific autoimmunity and tTreg cell production remains controversial...
December 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27538371/sarcoplasmic-reticulum-ca-2-atpase-2-serca2-reduces-the-migratory-capacity-of-ccl21-treated-monocyte-derived-dendritic-cells
#15
Cheol Yi Hong, Hyun-Ju Lee, Nu-Ri Choi, Sung-Hoon Jung, Manh-Cuong Vo, My Dung Hoang, Hyeoung-Joon Kim, Je-Jung Lee
The migration of dendritic cells (DCs) to secondary lymphoid organs depends on chemoattraction through the interaction of the chemokine receptors with chemokines. However, the mechanism of how lymphoid chemokines attract DCs to lymphoid organs remains unclear. Here, we demonstrate the mechanism of DC migration in response to the lymphoid chemokine CCL21. CCL21-mediated DC migration is controlled by the regulation of sarcoplasmic reticulum Ca(2+) ATPase 2 (SERCA2) expression rather than through the activation of mitogen-activated protein kinases CCL21-exposed mature DCs (mDCs) exhibited decreased SERCA2 expression but not decreased phospholamban (PLB) or Hax-1 expression, which are known to be SERCA2-interacting proteins...
2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27478837/the-hpv16-e7-oncoprotein-disrupts-dendritic-cell-function-and-induces-the-systemic-expansion-of-cd11b-gr1-cells-in-a-transgenic-mouse-model
#16
Gabriela Damian-Morales, Nicolás Serafín-Higuera, Mario Adán Moreno-Eutimio, Enoc M Cortés-Malagón, José Bonilla-Delgado, Genaro Rodríguez-Uribe, Rodolfo Ocadiz-Delgado, Paul F Lambert, Patricio Gariglio
Objective. The aim of this study was to analyze the effects of the HPV16 E7 oncoprotein on dendritic cells (DCs) and CD11b(+)Gr1(+) cells using the K14E7 transgenic mouse model. Materials and Methods. The morphology of DCs was analyzed in male mouse skin on epidermal sheets using immunofluorescence and confocal microscopy. Flow cytometry was used to determine the percentages of DCs and CD11b(+)Gr1(+) cells in different tissues and to evaluate the migration of DCs. Results. In the K14E7 mouse model, the morphology of Langerhans cells and the migratory activity of dendritic cells were abnormal...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27451948/human-breast-cancer-derived-soluble-factors-facilitate-ccl19-induced-chemotaxis-of-human-dendritic-cells
#17
Hyundoo Hwang, Changsik Shin, Juhee Park, Enoch Kang, Bongseo Choi, Jae-A Han, Yoonkyung Do, Seongho Ryu, Yoon-Kyoung Cho
Breast cancer remains as a challenging disease with high mortality in women. Increasing evidence points the importance of understanding a crosstalk between breast cancers and immune cells, but little is known about the effect of breast cancer-derived factors on the migratory properties of dendritic cells (DCs) and their consequent capability in inducing T cell immune responses. Utilizing a unique 3D microfluidic device, we here showed that breast cancers (MCF-7, MDA-MB-231, MDA-MB-436 and SK-BR-3)-derived soluble factors increase the migration of DCs toward CCL19...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27450002/tlr4-and-dc-sign-receptors-recognized-mycobacterium-scrofulaceum-promoting-semi-activated-phenotype-on-bone-marrow-dendritic-cells
#18
Marisa Cruz-Aguilar, Antonia I Castillo-Rodal, Alejandro Schcolnik-Cabrera, Laura C Bonifaz, Gabriela Molina, Yolanda López-Vidal
Nontuberculous mycobacteria (NTM) are recognized as emerging pathogens and their immune regulatory mechanisms are not well described yet. From them, Mycobacterium avium is known to be a weak activator of dendritic cells (DCs) that impairs the response induced by BCG vaccine. However, whether other NTM such as Mycobacterium scrofulaceum may modulate the activation of DCs, has not been extensively studied. Here, we exposed bone marrow-derived DCs (BMDCs) to M. scrofulaceum and we analyzed the effect on the activation of DCs...
July 2016: Tuberculosis
https://www.readbyqxmd.com/read/27446817/coxiella-burnetii-induces-inflammatory-interferon-like-signature-in-plasmacytoid-dendritic-cells-a-new-feature-of-immune-response-in-q-fever
#19
Mignane B Ka, Soraya Mezouar, Amira Ben Amara, Didier Raoult, Eric Ghigo, Daniel Olive, Jean-Louis Mege
Plasmacytoid dendritic cells (pDCs) play a major role in antiviral immunity via the production of type I interferons (IFNs). There is some evidence that pDCs interact with bacteria but it is not yet clear whether they are protective or contribute to bacterial pathogenicity. We wished to investigate whether Coxiella burnetii, the agent of Q fever, interacts with pDCs. The stimulation of pDCs with C. burnetii increased the expression of activation and migratory markers (CD86 and CCR7) as determined by flow cytometry and modulated gene expression program as revealed by a microarray approach...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27438481/rig-i-signaling-is-critical-for-efficient-polyfunctional-t-cell-responses-during-influenza-virus-infection
#20
Matheswaran Kandasamy, Amol Suryawanshi, Smanla Tundup, Jasmine T Perez, Mirco Schmolke, Santhakumar Manicassamy, Balaji Manicassamy
Retinoic acid inducible gene-I (RIG-I) is an innate RNA sensor that recognizes the influenza A virus (IAV) RNA genome and activates antiviral host responses. Here, we demonstrate that RIG-I signaling plays a crucial role in restricting IAV tropism and regulating host immune responses. Mice deficient in the RIG-I-MAVS pathway show defects in migratory dendritic cell (DC) activation, viral antigen presentation, and priming of CD8+ and CD4+ T cell responses during IAV infection. These defects result in decreased frequency of polyfunctional effector T cells and lowered protection against heterologous IAV challenge...
July 2016: PLoS Pathogens
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