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https://www.readbyqxmd.com/read/28802126/derp1-modified-dendritic-cells-attenuate-allergic-inflammation-by-regulating-the-development-of-t-helper-type1-th1-th2-cells-and-regulatory-t-cells-in-a-murine-model-of-allergic-rhinitis
#1
Shaoqing Yu, Bing Han, Shuangxi Liu, Hong Wang, Wenjie Zhuang, Yu Huang, Ruxin Zhang
The CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) are known to regulate Th2-induced allergic rhinitis (AR). In this study, we evaluated the efficacy of Derp1-modified dendritic cells (DCs) in AR immunotherapy. Derp1 was synthesized and transfected into DCs to generate Derp1-modified DCs. Phenotypes of Derp1-modified DCs were analyzed with flow cytometry using antibodies against DC markers CD11c, CD11b, CD59, CD103 and Toll-like receptor 1(TLR1). Four groups of subject mice were formed; the controls were treated with immature DCs, while the AR mice models were sensitized with Derp1(AR) and treated with DCs(DC-AR) or Derp1-modified DCs (Derp1DC-AR)...
August 9, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28798047/mtor-regulates-metabolic-adaptation-of-apcs-in-the-lung-and-controls-the-outcome-of-allergic-inflammation
#2
Charles Sinclair, Gayathri Bommakanti, Luiz Gardinassi, Jens Loebbermann, Matthew Joseph Johnson, Paul Hakimpour, Thomas Hagan, Lydia Benitez, Andrei Todor, Deepa Machiah, Timothy Oriss, Anuradha Ray, Steven Bosinger, Rajesh Ravindran, Shuzhao Li, Bali Pulendran
Antigen-presenting cells (APCs) occupy diverse anatomical tissues, but their tissue-restricted homeostasis remains poorly understood. Here, working in mouse models of inflammation, we found that mTOR-dependent metabolic adaptation was required at discrete locations. mTOR was dispensable for DC homeostasis in secondary lymphoid tissues but necessary to regulate cellular metabolism and accumulation of CD103(+) DCs and alveolar macrophages in lung. Moreover, while numbers of mTOR-deficient lung CD11b(+) DCs were not changed, they were metabolically reprogrammed to skew allergic inflammation from eosinophilic Th2 to neutrophilic Th17 polarity...
August 10, 2017: Science
https://www.readbyqxmd.com/read/28797734/microrna-150-controls-differentiation-of-intraepithelial-lymphocytes-via-tgf-%C3%AE-receptor-ii-regulation
#3
Sang-Hwan Seo, Min Seong Jang, Doo-Jin Kim, Seok-Min Kim, Se-Chan Oh, Cho-Rok Jung, Yunji Park, Sang-Jun Ha, Haiyoung Jung, Young-Jun Park, Suk Ran Yoon, Inpyo Choi, Tae-Don Kim
BACKGROUND: Intraepithelial lymphocytes (IELs) in the intestines play pivotal roles in maintaining the integrity of the mucosa, regulating the immune cells, and protecting against pathogenic invasion. Although several extrinsic factors such as transforming growth factor-β (TGF-β) have been identified to contribute to IEL generation, intrinsic regulatory factors have not been fully determined. OBJECTIVE: Here, we investigated the regulation of IEL differentiation and the underlying mechanisms in mice...
August 7, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28792004/adjuvant-selection-regulates-gut-migration-and-phenotypic-diversity-of-antigen-specific-cd4-t-cells-following-parenteral-immunization
#4
D R Frederick, J A Goggins, L M Sabbagh, L C Freytag, J D Clements, J B McLachlan
Infectious diarrheal diseases are the second leading cause of death in children under 5 years, making vaccines against these diseases a high priority. It is known that certain vaccine adjuvants, chiefly bacterial ADP-ribosylating enterotoxins, can induce mucosal antibodies when delivered parenterally. Based on this, we reasoned vaccine-specific mucosal cellular immunity could be induced via parenteral immunization with these adjuvants. Here, we show that, in contrast to the Toll-like receptor-9 agonist CpG, intradermal immunization with non-toxic double-mutant heat-labile toxin (dmLT) from enterotoxigenic Escherichia coli drove endogenous, antigen-specific CD4(+) T cells to expand and upregulate the gut-homing integrin α4β7...
August 9, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28772128/cytotoxic-tumour-infiltrating-t-lymphocytes-influence-outcome-in-resected-pancreatic-ductal-adenocarcinoma
#5
Philipp Lohneis, Marianne Sinn, Sven Bischoff, Anja Jühling, Uwe Pelzer, Lilianna Wislocka, Marcus Bahra, Bruno V Sinn, Carsten Denkert, Helmut Oettle, Hendrik Bläker, Hanno Riess, Korinna Jöhrens, Jana K Striefler
BACKGROUND: We studied the prognostic effect of CD3-, CD8- and CD103-positive T lymphocytes in a cohort of 165 patients with resected pancreatic ductal adenocarcinomas (PDACs) of the treatment group (adjuvant gemcitabine) and the untreated control group of the CONKO-001 study. METHODS: Immunohistochemical stainings on tissue microarrays (TMAs) against CD3, CD8 and CD103 were performed according to standard procedures. RESULTS: A high number of CD8-positive lymphocytes were significantly and independently associated with longer disease-free survival (DFS) and overall survival (OS) in the overall study population...
July 31, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28771609/deletion-of-batf3-dependent-antigen-presenting-cells-does-not-affect-atherosclerotic-lesion-formation-in-mice
#6
Jesus Gil-Pulido, Clement Cochain, Malte A Lippert, Nicole Schneider, Elke Butt, Núria Amézaga, Alma Zernecke
Atherosclerosis is the main underlying cause for cardiovascular events such as myocardial infarction and stroke and its development might be influenced by immune cells. Dendritic cells (DCs) bridge innate and adaptive immune responses by presenting antigens to T cells and releasing a variety of cytokines. Several subsets of DCs can be discriminated that engage specific transcriptional pathways for their development. Basic leucine zipper transcription factor ATF-like 3 (Batf3) is required for the development of classical CD8α+ and CD103+ DCs...
2017: PloS One
https://www.readbyqxmd.com/read/28766553/regulatory-t-cells-with-superior-immunosuppressive-capacity-emigrate-from-the-inflamed-colon-to-draining-lymph-nodes
#7
Y Nakanishi, R Ikebuchi, T Chtanova, Y Kusumoto, H Okuyama, T Moriya, T Honda, K Kabashima, T Watanabe, Y Sakai, M Tomura
Foxp3(+) Regulatory T cells (Tregs) play a critical role in the maintenance of colon homeostasis. Here we utilized photoconvertible KikGR mice to track immune cells from the caecum and ascending (proximal) colon in the steady state and DSS-induced colitis. We found that Tregs from the proximal colon (colonic migratory Tregs) migrated exclusively to the distal part of mesenteric lymph nodes (dMLN) in an S1PR1-dependent process. In the steady state, colonic migratory CD25(+) Tregs expressed higher levels of CD103, ICOS, LAG3 and CTLA-4 in comparison with pre-existing LN Tregs...
August 2, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28763795/intratumoral-delivery-of-inactivated-modified-vaccinia-virus-ankara-imva-induces-systemic-antitumor-immunity-via-sting-and-batf3-dependent-dendritic-cells
#8
Peihong Dai, Weiyi Wang, Ning Yang, Cristian Serna-Tamayo, Jacob M Ricca, Dmitriy Zamarin, Stewart Shuman, Taha Merghoub, Jedd D Wolchok, Liang Deng
Advanced cancers remain a therapeutic challenge despite recent progress in targeted therapy and immunotherapy. Novel approaches are needed to alter the tumor immunosuppressive microenvironment and to facilitate the recognition of tumor antigens that leads to antitumor immunity. Poxviruses, such as modified vaccinia virus Ankara (MVA), have potential as immunotherapeutic agents. We show that infection of conventional dendritic cells (DCs) with heat- or ultraviolet-inactivated MVA leads to higher levels of interferon induction than MVA alone through the cGAS (cyclic guanosine monophosphate-adenosine monophosphate synthase)-STING cytosolic DNA-sensing pathway...
May 19, 2017: Science Immunology
https://www.readbyqxmd.com/read/28763794/targeting-latency-associated-peptide-promotes-antitumor-immunity
#9
Galina Gabriely, Andre P da Cunha, Rafael M Rezende, Brendan Kenyon, Asaf Madi, Tyler Vandeventer, Nathaniel Skillin, Stephen Rubino, Lucien Garo, Maria A Mazzola, Panagiota Kolypetri, Amanda J Lanser, Thais Moreira, Ana Maria C Faria, Hans Lassmann, Vijay Kuchroo, Gopal Murugaiyan, Howard L Weiner
Regulatory T cells (Tregs) promote cancer by suppressing antitumor immune responses. We found that anti-LAP antibody, which targets the latency-associated peptide (LAP)/transforming growth factor-β (TGF-β) complex on Tregs and other cells, enhances antitumor immune responses and reduces tumor growth in models of melanoma, colorectal carcinoma, and glioblastoma. Anti-LAP decreases LAP(+) Tregs, tolerogenic dendritic cells, and TGF-β secretion and is associated with CD8(+) T cell activation. Anti-LAP increases infiltration of tumors by cytotoxic CD8(+) T cells and reduces CD103(+) CD8 T cells in draining lymph nodes and the spleen...
May 19, 2017: Science Immunology
https://www.readbyqxmd.com/read/28754680/versican-derived-matrikines-regulate-batf3-dendritic-cell-differentiation-and-promote-t-cell-infiltration-in-colorectal-cancer
#10
Chelsea Hope, Philip B Emmerich, Athanasios Papadas, Adam Pagenkopf, Kristina A Matkowskyj, Dana R Van De Hey, Susan N Payne, Linda Clipson, Natalie S Callander, Peiman Hematti, Shigeki Miyamoto, Michael G Johnson, Dustin A Deming, Fotis Asimakopoulos
Colorectal cancer originates within immunologically complex microenvironments. To date, the benefits of immunotherapy have been modest, except in neoantigen-laden mismatch repair-deficient tumors. Approaches to enhance tumor-infiltrating lymphocytes in the tumor bed may substantially augment clinical immunotherapy responses. In this article, we report that proteolysis of the tolerogenic matrix proteoglycan versican (VCAN) strongly correlated with CD8(+) T cell infiltration in colorectal cancer, regardless of mismatch repair status...
July 28, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28738020/resident-memory-t-cells-in-the-skin-mediate-durable-immunity-to-melanoma
#11
Brian T Malik, Katelyn T Byrne, Jennifer L Vella, Peisheng Zhang, Tamer B Shabaneh, Shannon M Steinberg, Aleksey K Molodtsov, Jacob S Bowers, Christina V Angeles, Chrystal M Paulos, Yina H Huang, Mary Jo Turk
Tissue-resident memory T (TRM) cells have been widely characterized in infectious disease settings; however, their role in mediating immunity to cancer remains unknown. We report that skin-resident memory T cell responses to melanoma are generated naturally as a result of autoimmune vitiligo. Melanoma antigen-specific TRM cells resided predominantly in melanocyte-depleted hair follicles and were maintained without recirculation or replenishment from the lymphoid compartment. These cells expressed CD103, CD69, and CLA (cutaneous lymphocyte antigen), but lacked PD-1 (programmed cell death protein-1) or LAG-3 (lymphocyte activation gene-3), and were capable of making IFN-γ (interferon-γ)...
April 14, 2017: Science Immunology
https://www.readbyqxmd.com/read/28733665/human-intrahepatic-cd69%C3%A2-%C3%A2-cd8-t-cells-have-a-tissue-resident-memory-t-cell-phenotype-with-reduced-cytolytic-capacity
#12
Femke Stelma, Annikki de Niet, Marjan J Sinnige, Karel A van Dort, Klaas P J M van Gisbergen, Joanne Verheij, Ester M M van Leeuwen, Neeltje A Kootstra, Hendrik W Reesink
Tissue resident memory T cells (TRM) have been identified in various tissues, however human liver TRM to date remain unidentified. TRM can be recognized by CD69 and/or CD103 expression and may play a role in the pathology of chronic hepatitis B (CHB) and hepatitis C virus infection (CHC). Liver and paired blood mononuclear cells from 17 patients (including 4 CHB and 6 CHC patients) were isolated and CD8+ T cells were comprehensively analysed by flowcytometry, immunohistochemistry and qPCR. The majority of intrahepatic CD8+ T cells expressed CD69, a marker used to identify TRM, of which a subset co-expressed CD103...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28707003/up-regulation-of-lfa-1-allows-liver-resident-memory-t-cells-to-patrol-and-remain-in-the-hepatic-sinusoids
#13
H A McNamara, Y Cai, M V Wagle, Y Sontani, C M Roots, L A Miosge, J H O'Connor, H J Sutton, V V Ganusov, W R Heath, P Bertolino, C G Goodnow, I A Parish, A Enders, I A Cockburn
Liver-resident CD8+ T cells are highly motile cells that patrol the vasculature and provide protection against liver pathogens. A key question is: how can these liver CD8+ T cells be simultaneously present in the circulation and tissue-resident? Because liver-resident T cells do not express CD103 - a key integrin for T cell residence in epithelial tissues - we investigated other candidate adhesion molecules. Using intra-vital imaging we found that CD8+ T cell patrolling in the hepatic sinusoids is dependent upon LFA-1-ICAM-1 interactions...
March 2017: Science Immunology
https://www.readbyqxmd.com/read/28700533/cd103-dendritic-cell-function-is-altered-in-the-colons-of-patients-with-ulcerative-colitis
#14
Hiroshi Matsuno, Hisako Kayama, Junichi Nishimura, Yuki Sekido, Hideki Osawa, Soumik Barman, Takayuki Ogino, Hidekazu Takahashi, Naotsugu Haraguchi, Taishi Hata, Chu Matsuda, Hirofumi Yamamoto, Motoi Uchino, Hiroki Ikeuchi, Yuichiro Doki, Masaki Mori, Kiyoshi Takeda, Tsunekazu Mizushima
BACKGROUND: Human intestinal innate myeloid cells can be divided into 3 subsets: HLA-DRCD14 cells, HLA-DRCD103 dendritic cells (DCs), and HLA-DRCD14CD103 cells. CD103 DCs generate Treg cells and Th17 cells in the ileum, but their function in the colon remains largely unknown. This study characterized CD103 DCs in the colon and investigated whether these cells are implicated in the pathogenesis of ulcerative colitis (UC). METHODS: Normal intestinal mucosa was obtained from intact sites of patients with colorectal cancer (n = 24)...
July 11, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28690613/relb-steady-state-migratory-dendritic-cells-control-the-peripheral-pool-of-the-natural-foxp3-regulatory-t-cells
#15
Anja Döhler, Theresa Schneider, Ina Eckert, Eliana Ribechini, Nico Andreas, Marc Riemann, Boris Reizis, Falk Weih, Manfred B Lutz
Thymus-derived natural Foxp3(+) CD4(+) regulatory T cells (nTregs) play a key role in maintaining immune tolerance and preventing autoimmune disease. Several studies indicate that dendritic cells (DCs) are critically involved in the maintenance and proliferation of nTregs. However, the mechanisms how DCs manage to keep the peripheral pool at constant levels remain poorly understood. Here, we describe that the NF-κB/Rel family transcription factor RelB controls the frequencies of steady-state migratory DCs (ssmDCs) in peripheral lymph nodes and their numbers control peripheral nTreg homeostasis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28671985/dectin-2-is-a-primary-receptor-for-nlrp3-inflammasome-activation-in-dendritic-cell-response-to-histoplasma-capsulatum
#16
Tzu-Hsuan Chang, Juin-Hua Huang, Hsiu-Chao Lin, Wen-Yu Chen, Yu-Hsiang Lee, Li-Chung Hsu, Mihai G Netea, Jenny P-Y Ting, Betty A Wu-Hsieh
Inflammasome is an intracellular protein complex that serves as cytosolic pattern recognition receptor (PRR) to engage with pathogens and to process cytokines of the interleukin-1 (IL-1) family into bioactive molecules. It has been established that interleukin-1β (IL-1β) is important to host defense against Histoplasma capsulatum infection. However, the detailed mechanism of how H. capsulatum induces inflammasome activation leading to IL-1β production has not been studied. Here, we showed in dendritic cells (DCs) that H...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28665959/increased-migration-of-antigen-presenting-cells-to-newly-formed-lymphatic-vessels-in-transplanted-kidneys-by-glycol-split-heparin
#17
Ditmer T Talsma, Kirankumar Katta, Miriam Boersema, Saritha Adepu, Annamaria Naggi, Giangiacomo Torri, Coen Stegeman, Gerjan Navis, Harry van Goor, Jan-Luuk Hillebrands, Saleh Yazdani, Jacob van den Born
BACKGROUND: Chronic renal transplant dysfunction is characterized by loss of renal function and tissue remodeling, including chronic inflammation and lymph vessel formation. Proteoglycans are known for their chemokine presenting capacity. We hypothesize that interruption of the lymphatic chemokine-proteoglycan interaction interferes with the lymphatic outflow of leukocytes from the renal graft and might decrease the anti-graft allo-immune response. METHODS: In a rat renal chronic transplant dysfunction model (female Dark-Agouti to male Wistar Furth), chemokines were profiled by qRT-PCR in microdissected tubulo-interstitial tissue...
2017: PloS One
https://www.readbyqxmd.com/read/28652304/thymic-progenitors-of-tcr%C3%AE-%C3%AE-cd8%C3%AE-%C3%AE-intestinal-intraepithelial-lymphocytes-require-rasgrp1-for-development
#18
Dominic P Golec, Romy E Hoeppli, Laura M Henao Caviedes, Jillian McCann, Megan K Levings, Troy A Baldwin
Strong T cell receptor (TCR) signaling largely induces cell death during thymocyte development, whereas weak TCR signals induce positive selection. However, some T cell lineages require strong TCR signals for differentiation through a process termed agonist selection. The signaling relationships that underlie these three fates are unknown. RasGRP1 is a Ras activator required to transmit weak TCR signals leading to positive selection. Here, we report that, despite being dispensable for thymocyte clonal deletion, RasGRP1 is critical for agonist selection of TCRαβ(+)CD8αα intraepithelial lymphocyte (IEL) progenitors (IELps), even though both outcomes require strong TCR signaling...
August 7, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28638851/mucosal-biopsy-shows-immunologic-changes-of-the-colon-in-patients-with-early-ms
#19
Adrian Mathias Moser, Walter Spindelboeck, Heimo Strohmaier, Christian Enzinger, Thomas Gattringer, Siegrid Fuchs, Franz Fazekas, Gregor Gorkiewicz, Philipp Wurm, Christoph Högenauer, Michael Khalil
OBJECTIVE: To investigate immune cells of the colonic mucosa and fecal short-chain fatty acids (SCFAs) in treatment-naive patients with a clinically isolated syndrome (CIS) or early relapsing MS. METHODS: In this cross-sectional proof-of-concept study, we obtained mucosal specimens during ileocolonoscopy from 15 untreated patients with CIS/MS and 10 controls. Mucosal immune cells were analyzed by FACS, and gas chromatography-mass spectrometry measurements of stool samples served to determine SCFA...
July 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/28628641/hypersensitivity-pneumonitis-onset-and-severity-is-regulated-by-cd103-dendritic-cell-expression
#20
Emilie Bernatchez, Anick Langlois, Julyanne Brassard, Nicolas Flamand, David Marsolais, Marie-Renée Blanchet
BACKGROUND: Pulmonary dendritic cells drive lung responses to foreign antigens, including Saccharopolyspora rectivirgula, a causative agent of hypersensitivity pneumonitis. While the airway inflammatory mechanisms involved in hypersensitivity pneumonitis are well described, the mechanisms leading to the break in homeostasis and hypersensitivity pneumonitis onset are not well-described, and could involve CD103+ dendritic cells, which are found at baseline and during inflammatory responses in the lung...
2017: PloS One
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