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https://www.readbyqxmd.com/read/29316433/tim-3-regulates-cd103-dendritic-cell-function-and-response-to-chemotherapy-in-breast-cancer
#1
Álvaro de Mingo Pulido, Alycia Gardner, Shandi Hiebler, Hatem Soliman, Hope S Rugo, Matthew F Krummel, Lisa M Coussens, Brian Ruffell
Intratumoral CD103+ dendritic cells (DCs) are necessary for anti-tumor immunity. Here we evaluated the expression of immune regulators by CD103+ DCs in a murine model of breast cancer and identified expression of TIM-3 as a target for therapy. Anti-TIM-3 antibody improved response to paclitaxel chemotherapy in models of triple-negative and luminal B disease, with no evidence of toxicity. Combined efficacy was CD8+ T cell dependent and associated with increased granzyme B expression; however, TIM-3 expression was predominantly localized to myeloid cells in both human and murine tumors...
January 8, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29314633/leucocyte-and-platelet-rich-fibrin-a-carrier-of-autologous-multipotent-cells-for-regenerative-medicine
#2
Rosa Di Liddo, Thomas Bertalot, Alessio Borean, Ivan Pirola, Alberto Argentoni, Sandra Schrenk, Carola Cenzi, Stefano Capelli, Maria Teresa Conconi, Pier Paolo Parnigotto
The wound healing is a complex process wherein inflammation, proliferation and regeneration evolve according to a spatio-temporal pattern from the activation of coagulation cascade to the formation of a plug clot including fibrin matrix, blood-borne cells and cytokines/growth factors. Creating environments conducive to tissue repair, the haemoderivatives are commonly proposed for the treatment of hard-to-heal wounds. Here, we explored in vitro the intrinsic regenerative potentialities of a leucocyte- and platelet-rich fibrin product, known as CPL-MB, defining the stemness grade of cells sprouting from the haemoderivative...
January 5, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29311150/correction-irf4-dependent-cd103-cd11b-dendritic-cells-and-the-intestinal-microbiome-regulate-monocyte-and-macrophage-activation-and-intestinal-peristalsis-in-postoperative-ileus
#3
https://www.readbyqxmd.com/read/29288569/sex-based-differences-in-cd103-dendritic-cells-promote-female-predominant-th2-cytokine-production-during-allergic-asthma
#4
Chiaki Masuda, Tomomitsu Miyasaka, Kaori Kawakami, Jin-Ichi Inokuchi, Tasuku Kawano, Kaori Dobashi-Okuyama, Tomoko Takahashi, Motoaki Takayanagi, Isao Ohno
BACKGROUND: Gender disparities in adult patients with asthma regarding its prevalence and severity are mainly due to enhanced type 2 T-helper (Th2) cytokine production in female patients compared to that in male patients. However, the pathways mediating this effect remain unclear. OBJECTIVE: We aimed to determine the roles of two major subsets of dendritic cells (DCs) in females, specifically those displaying CD11b or CD103, during enhanced Th2-priming after allergen exposure, using an ovalbumin-induced asthma mouse model...
December 30, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29281833/nlrp3-controls-the-development-of-gastrointestinal-cd11b-dendritic-cells-in-the-steady-state-and-during-chronic-bacterial-infection
#5
Isabelle C Arnold, Xiaozhou Zhang, Sabine Urban, Mariela Artola-Borán, Markus G Manz, Karen M Ottemann, Anne Müller
The gastric lamina propria is largely uncharted immunological territory. Here we describe the evolution and composition of the gastric, small intestinal, and colonic lamina propria mononuclear phagocyte system during the steady state and infection with the gastric pathogen Helicobacter pylori. We show that monocytes, CX3CR1hi macrophages, and CD11b+ dendritic cells are recruited to the infected stomach in a CCR2-dependent manner. All three populations, but not BATF3-dependent CD103+ DCs, sample red fluorescent protein (RFP)+Helicobacter pylori (H...
December 26, 2017: Cell Reports
https://www.readbyqxmd.com/read/29241547/car-t-cells-releasing-il-18-convert-to-t-bethigh-foxo1low-effectors-that-exhibit-augmented-activity-against-advanced-solid-tumors
#6
Markus Chmielewski, Hinrich Abken
Adoptive therapy with chimeric antigen receptor (CAR)-redirected T cells has achieved remarkable efficacy in the treatment of hematopoietic malignancies. However, eradicating large solid tumors in advanced stages of the disease remains challenging. We explored augmentation of the anti-tumor immune reaction by establishing an acute inflammatory reaction. Systematic screening indicates that IL-18 polarizes CAR T cells toward T-bethigh FoxO1low effectors with an acute inflammatory response. CAR T cells engineered with inducible IL-18 release exhibited superior activity against large pancreatic and lung tumors that were refractory to CAR T cells without cytokines...
December 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/29228157/gut-epithelial-vitamin-d-receptor-regulates-microbiota-dependent-mucosal-inflammation-by-suppressing-intestinal-epithelial-cell-apoptosis
#7
Lei He, Tianjing Liu, Yongyan Shi, Feng Tian, Huiyuan Hu, Dilip K Deb, Yinyin Chen, Marc Bissonnette, Yan Chun Li
Recent studies show that colonic vitamin D receptor (VDR) signaling protects the mucosal epithelial barrier and suppresses colonic inflammation, but the underlying molecular mechanism remains to be fully understood. To investigate the implication of colonic VDR down-regulation seen in patients with inflammatory bowel disease, we assessed the effect of gut epithelial VDR deletion on colonic inflammatory responses in an experimental colitis model. In 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis model, mice carrying VDR deletion in gut epithelial cells (VDRf/f;Villin-Cre or VDRΔIEC) or in colonic epithelial cells (VDRf/f;CDX2-Cre or VDRΔCEC) developed more severe clinical colitis than VDRf/f control mice, characterized by more robust TH1 and TH17 responses, with greater increases in mucosal IFN-γ+, IL-17+ and IFN-γ+IL-17+ T cells...
December 7, 2017: Endocrinology
https://www.readbyqxmd.com/read/29220358/minimally-invasive-monitoring-of-cd4-t-cells-at-multiple-mucosal-tissues-after-intranasal-vaccination-in-rhesus-macaques
#8
Stephanie Dorta-Estremera, Pramod N Nehete, Guojun Yang, Hong He, Bharti P Nehete, Kathryn K Shelton, Michael A Barry, K Jagannadha Sastry
Studies in nonhuman primates (NHP) for prospective immune cell monitoring subsequent to infection and/or vaccination usually rely on periodic sampling of the blood samples with only occasional collections of biopsies from mucosal tissues because of safety concerns and practical constraints. Here we present evidence in support of cytobrush sampling of oral, rectal, and genital mucosal tissues as a minimally invasive approach for the phenotypic analyses of different T cells subsets de novo as well as prospectively after intranasal immunization in rhesus macaques...
2017: PloS One
https://www.readbyqxmd.com/read/29217759/opposing-roles-of-dendritic-cell-subsets-in-experimental-gn
#9
Sebastian Brähler, Bernd H Zinselmeyer, Saravanan Raju, Maximilian Nitschke, Hani Suleiman, Brian T Saunders, Michael W Johnson, Alexander M C Böhner, Susanne F Viehmann, Derek J Theisen, Nicole M Kretzer, Carlos G Briseño, Konstantin Zaitsev, Olga Ornatsky, Qing Chang, Javier A Carrero, Jeffrey B Kopp, Maxim N Artyomov, Christian Kurts, Kenneth M Murphy, Jeffrey H Miner, Andrey S Shaw
Dendritic cells (DCs) are thought to form a dendritic network across barrier surfaces and throughout organs, including the kidney, to perform an important sentinel function. However, previous studies of DC function used markers, such as CD11c or CX3CR1, that are not unique to DCs. Here, we evaluated the role of DCs in renal inflammation using a CD11c reporter mouse line and two mouse lines with DC-specific reporters, Zbtb46-GFP and Snx22-GFP. Multiphoton microscopy of kidney sections confirmed that most of the dendritically shaped CD11c+ cells forming a network throughout the renal interstitium expressed macrophage-specific markers...
December 7, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29212947/requirement-of-treg-intrinsic-ctla4-pkc%C3%AE-signaling-pathway-for-suppressing-tumor-immunity
#10
Christophe Pedros, Ann J Canonigo-Balancio, Kok-Fai Kong, Amnon Altman
The ability of Tregs to control the development of immune responses is essential for maintaining immune system homeostasis. However, Tregs also inhibit the development of efficient antitumor responses. Here, we explored the characteristics and mechanistic basis of the Treg-intrinsic CTLA4/PKCη signaling pathway that we recently found to be required for contact-dependent Treg-mediated suppression. We show that PKCη is required for the Treg-mediated suppression of tumor immunity in vivo. The presence of PKCη-deficient (Prkch-/-) Tregs in the tumor microenvironment was associated with a significantly increased expression of the costimulatory molecule CD86 on intratumoral CD103+ DCs, enhanced priming of antigen-specific CD8+ T cells, and greater levels of effector cytokines produced by these cells...
December 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/29211912/intestinal-t-cell-profiling-in-inflammatory-bowel-disease-linking-t-cell-subsets-to-disease-activity-and-disease-course
#11
Carolijn Smids, Carmen S Horjus Talabur Horje, Julia Drylewicz, Britt Roosenboom, Marcel J M Groenen, Elly van Koolwijk, Ellen G van Lochem, Peter J Wahab
Introduction: A dysregulated intestinal T-cell response is presumed in patients with Inflammatory Bowel Disease (IBD). In this longitudinal study, we investigated the changes in intestinal T lymphocyte subsets in IBD at first presentation and over time during endoscopic active or inactive disease and relate them to disease activity and outcome. Material & method: We included 129 newly diagnosed patients (87 Crohn´s Disease (CD), 42 ulcerative colitis (UC)) and 19 healthy controls (HC)...
December 4, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/29203869/trpm7-kinase-activity-is-essential-for-t-cell-colonization-and-alloreactivity-in-the-gut
#12
Andrea Romagnani, Valentina Vettore, Tanja Rezzonico-Jost, Sarah Hampe, Elsa Rottoli, Wiebke Nadolni, Michela Perotti, Melanie A Meier, Constanze Hermanns, Sheila Geiger, Gunther Wennemuth, Camilla Recordati, Masayuki Matsushita, Susanne Muehlich, Michele Proietti, Vladimir Chubanov, Thomas Gudermann, Fabio Grassi, Susanna Zierler
The melastatin-like transient-receptor-potential-7 protein (TRPM7), harbouring a cation channel and a serine/threonine kinase, has been implicated in thymopoiesis and cytokine expression. Here we show, by analysing TRPM7 kinase-dead mutant (Trpm7 R/R ) mice, that the enzymatic activity of the receptor is not essential for thymopoiesis, but is required for CD103 transcription and gut-homing of intra-epithelial lymphocytes. Defective T cell gut colonization reduces MHCII expression in intestinal epithelial cells...
December 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/29197137/immunohistopathological-characterization-and-the-impact-of-topical-immunomodulatory-therapy-in-oral-chronic-gvhd-a-pilot-study
#13
Ana Carolina F Motta, Qian Zhan, Allison Larson, Mark Lerman, Sook-Bin Woo, Robert J Soiffer, George F Murphy, Nathaniel S Treister
OBJECTIVE: To characterize the immunohistopathologic features of oral chronic graft-versus-host disease (cGVHD), and the impact of topical immunomodulatory therapy on the infiltrating cells. MATERIAL AND METHODS: Paired oral cGVHD biopsies obtained before (n=12) and one month after treatment (n=12) with topical dexamethasone (n=8) or tacrolimus (n=4) were characterized by immunohistochemistry using a panel of CD1a, CD3, CD4, CD8, CD20, CD31, CD62E, CD103, CD163, c-kit and FoxP3...
December 2, 2017: Oral Diseases
https://www.readbyqxmd.com/read/29196458/integrin-%C3%AE-4%C3%AE-7-blockade-preferentially-impacts-ccr6-lymphocyte-subsets-in-blood-and-mucosal-tissues-of-naive-rhesus-macaques
#14
Giulia Calenda, Rassamon Keawvichit, Géraldine Arrode-Brusés, Kovit Pattanapanyasat, Ines Frank, Siddappa N Byrareddy, James Arthos, Claudia Cicala, Brooke Grasperge, James L Blanchard, Agegnehu Gettie, Keith A Reimann, Aftab A Ansari, Elena Martinelli
Infusion of a simianized anti-α4β7 mAb (Rh-α4β7) just before and following SIV infection protected rhesus macaques from developing AIDS and partially from vaginal SIV acquisition. Recently, short-term treatment with Rh-α4β7 in combination with cART was found to lead to prolonged viral suppression after withdrawal of all therapeutic interventions. The humanized form of Rh-α4β7, vedolizumab, is a highly effective treatment for inflammatory bowel disease. To clarify the mechanism of action of Rh-α4β7, naive macaques were infused with Rh-α4β7 and sampled in blood and tissues before and after treatment to monitor several immune cell subsets...
December 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29196450/migratory-cd11b-conventional-dendritic-cells-induce-t-follicular-helper-cell-dependent-antibody-responses
#15
Jayendra Kumar Krishnaswamy, Uthaman Gowthaman, Biyan Zhang, Johan Mattsson, Louis Szeponik, Dong Liu, Renee Wu, Theresa White, Samuele Calabro, Lan Xu, Magalie A Collet, Marina Yurieva, Samuel Alsén, Per Fogelstrand, Anne Walter, William R Heath, Scott N Mueller, Ulf Yrlid, Adam Williams, Stephanie C Eisenbarth
T follicular helper (Tfh) cells are a subset of CD4+ T cells that promote antibody production during vaccination. Conventional dendritic cells (cDCs) efficiently prime Tfh cells; however, conclusions regarding which cDC instructs Tfh cell differentiation have differed between recent studies. We found that these discrepancies might exist because of the unusual sites used for immunization in murine models, which differentially bias which DC subsets access antigen. We used intranasal immunization as a physiologically relevant route of exposure that delivers antigen to all tissue DC subsets...
December 1, 2017: Science Immunology
https://www.readbyqxmd.com/read/29194570/characterization-of-cd45ro-memory-t-lymphocytes-in-keloid-disease
#16
Z Chen, L Zhou, T Won, Z Gao, X Wu, L Lu
BACKGROUND: Memory T cells, a highly effective subset of T lymphocytes, have been reported to be involved in many inflammatory skin disorders. However, the potential role of memory T cells in keloid disease (KD) remains unclear. OBJECTIVES: Due to their important role in regulating inflammation, we investigated the characteristics of CD45RO+ memory T cells (mT) in KD. METHODS: Primary cutaneous cells were isolated from keloid scars and normal skin by enzymic digestion...
December 1, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/29190678/type-i-interferon-signaling-restrains-il-10r-colonic-macrophages-and-dendritic-cells-and-leads-to-more-severe-salmonella-colitis
#17
Kailyn L Stefan, Avner Fink, Neeraj K Surana, Dennis L Kasper, Suryasarathi Dasgupta
Type I interferons (IFNα, IFNβ) are key regulators of innate and adaptive immunity, modulating the severity of both viral and bacterial infections. While type I IFN signaling leads to improved outcomes in viral infections, its role in bacterial infections is more contextual and depends on the specific pathogen and route of infection. Given the limited evidence on whether type I IFN signaling affects enteric bacterial pathogens, we investigated the role of this signaling pathway in Salmonella enterica serovar Typhimurium (S...
2017: PloS One
https://www.readbyqxmd.com/read/29180478/perioperative-spatiotemporally-coordinated-activation-of-t-and-nk-cells-prevents-recurrence-of-pancreatic-cancer
#18
Jennifer Brooks, Bettina Fleischmann-Mundt, Norman Woller, Julia Niemann, Silvia Ribback, Kristin Peters, Ihsan Ekin Demir, Nina Armbrecht, Guralp O Ceyhan, Michael P Manns, Thomas C Wirth, Stefan Kubicka, Gunter Bernhardt, Mark J Smyth, Diego F Calvisi, Engin Gürlevik, Florian Kühnel
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal and disseminating cancer resistant to therapy, including checkpoint immunotherapies, and early tumor resection and (neo)adjuvant chemotherapy fails to improve a poor prognosis. In a transgenic mouse model of resectable PDAC, we investigated the coordinated activation of T and NK cells in addition to gemcitabine chemotherapy to prevent tumor recurrence. Only neoadjuvant, but not adjuvant treatment with a PD-1 antagonist effectively supported chemotherapy and suppressed local tumor recurrence and improved survival involving both NK and T cells...
November 27, 2017: Cancer Research
https://www.readbyqxmd.com/read/29176981/bifidobacterium-infantis-potentially-alleviates-shrimp-tropomyosin-induced-allergy-by-tolerogenic-dendritic-cell-dependent-induction-of-regulatory-t-cells-and-alterations-in-gut-microbiota
#19
Linglin Fu, Jinyu Song, Chong Wang, Shujie Fu, Yanbo Wang
Shellfish is one of the major allergen sources worldwide, and tropomyosin (Tm) is the predominant allergic protein in shellfish. Probiotics has been appreciated for its beneficial effects on the host, including anti-allergic and anti-inflammatory effects, although the underlying mechanisms were not fully understood. In this study, oral administration of probiotic strain Bifidobacterium infantis 14.518 (Binf) effectively suppressed Tm-induced allergic response in a mouse model by both preventive and therapeutic strategies...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29170671/b7-h1-influences-the-accumulation-of-virus-specific-tissue-resident-memory-t-cells-in-the-central-nervous-system
#20
Kevin D Pavelko, Michael P Bell, Susan M Harrington, Haidong Dong
Therapies that target the PD-1/B7-H1 axis have revolutionized cancer treatment, yet precise knowledge of how this pathway provides benefit continues to evolve. Here, we report a novel role for the immune checkpoint ligand B7-H1 in the accumulation of tissue-resident memory CD8(+) T-cells (TRM). After intracranial infection, Theiler's murine encephalomyelitis virus (TMEV) generates TRM that are maintained in the central nervous system (CNS) tissues of B7-H1(WT) animals. Although no differences in acute T-cell responses between B7-H1(WT) and B7-H1(KO) are observed, at long-term periods post-infection the maintenance of CD8(+) TRM is diminished in B7-H1(KO) animals...
2017: Frontiers in Immunology
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