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https://www.readbyqxmd.com/read/29467328/allograft-dendritic-cell-p40-homodimers-activate-donor-reactive-memory-cd8-t-cells
#1
Hidetoshi Tsuda, Charles A Su, Toshiaki Tanaka, Katayoun Ayasoufi, Booki Min, Anna Valujskikh, Robert L Fairchild
Recipient endogenous memory T cells with donor reactivity pose an important barrier to successful transplantation and costimulatory blockade-induced graft tolerance. Longer ischemic storage times prior to organ transplantation increase early posttransplant inflammation and negatively impact early graft function and long-term graft outcome. Little is known about the mechanisms enhancing endogenous memory T cell activation to mediate tissue injury within the increased inflammatory environment of allografts subjected to prolonged cold ischemic storage (CIS)...
February 22, 2018: JCI Insight
https://www.readbyqxmd.com/read/29456540/kallikrein-kinin-system-suppresses-type-i-interferon-responses-a-novel-pathway-of-interferon-regulation
#2
Alecia Seliga, Michael Hweemoon Lee, Nicole C Fernandes, Viviana Zuluaga-Ramirez, Marta Didukh, Yuri Persidsky, Raghava Potula, Stefania Gallucci, Uma Sriram
The Kallikrein-Kinin System (KKS), comprised of kallikreins (klks), bradykinins (BKs) angiotensin-converting enzyme (ACE), and many other molecules, regulates a number of physiological processes, including inflammation, coagulation, angiogenesis, and control of blood pressure. In this report, we show that KKS regulates Type I IFN responses, thought to be important in lupus pathogenesis. We used CpG (TLR9 ligand), R848 (TLR7 ligand), or recombinant IFN-α to induce interferon-stimulated genes (ISGs) and proteins, and observed that this response was markedly diminished by BKs, klk1 (tissue kallikrein), or captopril (an ACE inhibitor)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29446738/how-do-dendritic-cells-play-the-role-in-ischemia-reperfusion-triggered-kidney-allograft-rejection
#3
Songjie Cai, Naotsugu Ichimaru, Shiro Takahara
In deceased donors, ischemia/reperfusion injury (IRI) is an important cause of allograft dysfunction. Prolonged cold and warm ischemia time leads to a high risk of early post-transplant complications, including acute and chronic rejection. Ischemia not only up-regulates inflammatory cytokines and chemokines, but also enhances the expression of MHC-class II and adhesion molecules on epithelial and dendritic cells. Moreover, the danger associated molecular patterns (DAMPs) released from stressed or dying cells, not only cause or amplify tissue inflammation and trigger tissue repair in response to IRI, but also act as adjuvants that enhance DC maturation and potentiate the adaptive immune response...
February 13, 2018: Current Gene Therapy
https://www.readbyqxmd.com/read/29405379/mucosal-associated-invariant-t-cells-in-autoimmune-and-immune-mediated-diseases
#4
Ophélie Rouxel, Agnès Lehuen
Autoimmune and inflammatory diseases have complex etiologies not fully understood. Both innate and adaptive immune cells are involved in the pathogenesis of these diseases. Mucosal-associated invariant (MAI)T cells express an invariant TCRα chain (Vα7.2-Jα33 in humans and Vα19-Jα33 in mice) and recognize the conserved MHC-I related molecule MR1 presenting bacterial metabolites derived from the synthesis of vitamin B. MAIT cells harbor tissue homing properties and produce inflammatory cytokines suggesting that MAIT cells may play a key role in autoimmune and inflammatory diseases...
February 6, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29393209/therapeutic-role-for-tsp-2-antibody-in-a-murine-asthma-model
#5
Kai Li, En Ping Huang, Jin Su, Ping Zhu, Jun Lin, Shen Qiu Luo, Cui Lan Yang
BACKGROUND: Specific immunotherapy, including agonists for Toll-like receptor 2 (TLR2), have been shown to protect from allergies and to have a high immunomodulatory capacity. METHODS: A new antibody, TSP-2, reactive against an epitope of the extracellular domain of TLR2, was identified. The effect of the antibody on dendritic cells was assessed by immunohistochemistry, Western blot, and flow cytometric analysis. The effect of TSP-2 in a murine asthma model induced with ovalbumin (OVA) was assessed...
January 27, 2018: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/29376889/batf-dependent-il-7rhigm-csf-t-cells-control-intestinal-graft-versus-host-disease
#6
Evelyn Ullrich, Benjamin Abendroth, Johanna Rothamer, Carina Huber, Maike Büttner-Herold, Vera Buchele, Tina Vogler, Thomas Longerich, Sebastian Zundler, Simon Völkl, Andreas Beilhack, Stefan Rose-John, Stefan Wirtz, Georg F Weber, Sakhila Ghimire, Marina Kreutz, Ernst Holler, Andreas Mackensen, Markus F Neurath, Kai Hildner
Acute graft-versus-host disease (GVHD) represents a severe, T cell-driven inflammatory complication following allogeneic hematopoietic cell transplantation (allo-HCT). GVHD often affects the intestine and is associated with a poor prognosis. Although frequently detectable, proinflammatory mechanisms exerted by intestinal tissue-infiltrating Th cell subsets remain to be fully elucidated. Here, we show that the Th17-defining transcription factor basic leucine zipper transcription factor ATF-like (BATF) was strongly regulated across human and mouse intestinal GVHD tissues...
January 29, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29363184/functional-differences-in-airway-dendritic-cells-determine-susceptibility-to-ige-sensitisation
#7
Jonatan Leffler, Kyle T Mincham, Danny Mok, Fabian Blank, Patrick G Holt, Philip A Stumbles, Deborah H Strickland
Respiratory IgE-sensitisation to innocuous antigens increases the risk for developing diseases such as allergic asthma. Dendritic cells (DC) residing in the airways orchestrate the immune response following antigen exposure and their ability to sample and present antigens to naïve T cells in airway draining lymph nodes contributes to allergen-specific IgE-sensitisation. In order to characterise inhaled antigen capture and presentation by DC subtypes in vivo, we used an adjuvant-free respiratory sensitisation model using two genetically distinct rat strains, one of which is naturally resistant and the other naturally susceptible to allergic sensitisation...
December 30, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29361739/human-mhc-ii-with-shared-epitope-motifs-are-optimal-epstein-barr-virus-glycoprotein-42-ligands-relation-to-rheumatoid-arthritis
#8
REVIEW
Nicole Trier, Jose Izarzugaza, Anna Chailyan, Paolo Marcatili, Gunnar Houen
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder of unknown etiology, which is characterized by inflammation in the synovium and joint damage. Although the pathogenesis of RA remains to be determined, a combination of environmental (e.g., viral infections) and genetic factors influence disease onset. Especially genetic factors play a vital role in the onset of disease, as the heritability of RA is 50-60%, with the human leukocyte antigen (HLA) alleles accounting for at least 30% of the overall genetic risk...
January 21, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29358051/non-classical-immunity-controls-microbiota-impact-on-skin-immunity-and-tissue-repair
#9
Jonathan L Linehan, Oliver J Harrison, Seong-Ji Han, Allyson L Byrd, Ivan Vujkovic-Cvijin, Alejandro V Villarino, Shurjo K Sen, Jahangheer Shaik, Margery Smelkinson, Samira Tamoutounour, Nicholas Collins, Nicolas Bouladoux, Amiran Dzutsev, Stephan P Rosshart, Jesse H Arbuckle, Chyung-Ru Wang, Thomas M Kristie, Barbara Rehermann, Giorgio Trinchieri, Jason M Brenchley, John J O'Shea, Yasmine Belkaid
Mammalian barrier surfaces are constitutively colonized by numerous microorganisms. We explored how the microbiota was sensed by the immune system and the defining properties of such responses. Here, we show that a skin commensal can induce T cell responses in a manner that is restricted to non-classical MHC class I molecules. These responses are uncoupled from inflammation and highly distinct from pathogen-induced cells. Commensal-specific T cells express a defined gene signature that is characterized by expression of effector genes together with immunoregulatory and tissue-repair signatures...
January 15, 2018: Cell
https://www.readbyqxmd.com/read/29339738/dna-methyltransferase-inhibition-upregulates-mhc-i-to-potentiate-cytotoxic-t-lymphocyte-responses-in-breast-cancer
#10
Na Luo, Mellissa J Nixon, Paula I Gonzalez-Ericsson, Violeta Sanchez, Susan R Opalenik, Huili Li, Cynthia A Zahnow, Michael L Nickels, Fei Liu, Mohammed N Tantawy, Melinda E Sanders, H Charles Manning, Justin M Balko
Potentiating anti-tumor immunity by inducing tumor inflammation and T cell-mediated responses are a promising area of cancer therapy. Immunomodulatory agents that promote these effects function via a wide variety of mechanisms, including upregulation of antigen presentation pathways. Here, we show that major histocompatibility class-I (MHC-I) genes are methylated in human breast cancers, suppressing their expression. Treatment of breast cancer cell lines with a next-generation hypomethylating agent, guadecitabine, upregulates MHC-I expression in response to interferon-γ...
January 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29309749/patients-with-idiopathic-endplate-inflammation-displayed-aberrant-th17-responses-resulting-in-proinflammatory-monocyte-activation
#11
Jian Wang, Wanju Sun, Allen Bond, Chengpin Xu, Kai Li, Donglin Ren, Xin Song, Fang Tan, Kun Jiao, Mingfei Wang
Endplate inflammation remains a difficult task to diagnose and treat, partly due to the absence of in-depth understanding of the cellular and molecular factors driving this condition. In the current study, we investigated the circulating immune cells in patients with idiopathic endplate inflammation. Compared to healthy controls, the patients with endplate inflammation presented a significant upregulation of Th17 cells, characterized by higher frequencies of circulating IL-17+CD4+ T cells examined directly ex vivo and after PMA and ionomycin (PMA/I) stimulation...
January 5, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29305625/ifn-%C3%AE-induces-a-preferential-long-lasting-expression-of-mhc-class-i-in-human-pancreatic-beta-cells
#12
Alexandra Coomans de Brachène, Reinaldo S Dos Santos, Laura Marroqui, Maikel L Colli, Lorella Marselli, Raghavendra G Mirmira, Piero Marchetti, Decio L Eizirik
AIMS/HYPOTHESIS: IFN-α, a cytokine expressed in human islets from individuals affected by type 1 diabetes, plays a key role in the pathogenesis of diabetes by upregulating inflammation, endoplasmic reticulum (ER) stress and MHC class I overexpression, three hallmarks of islet histology in early type 1 diabetes. We tested whether expression of these mediators of beta cell loss is reversible upon IFN-α withdrawal or IFN-α pathway inhibition. METHODS: IFN-α-induced MHC class I overexpression, ER stress and inflammation were evaluated by flow cytometry, immunofluorescence and real-time PCR in human EndoC-βH1 cells or human islets exposed to IFN-α with or without the presence of Janus kinase (JAK) inhibitors...
January 5, 2018: Diabetologia
https://www.readbyqxmd.com/read/29273368/enhanced-vascular-regeneration-with-chemically-physically-treated-bovine-human-pericardium-in-rodents
#13
Mathieu van Steenberghe, Thomas Schubert, Daela Xhema, Caroline Bouzin, Yves Guiot, Jérôme Duisit, Karim Abdelhamid, Pierre Gianello
BACKGROUND: Glutaraldehyde-treated pericardia for cardiovascular applications have poor long-term clinical results. The efficacy of a combined physical/chemical treatment to improve pericardium biocompatibility and vascular regeneration was assessed and compared with detergent treatment and two commercial bovine pericardia: PeriGuard (DGBP) and Edwards pericardium (nDGBP). The physical and chemical process was applied to bovine and human pericardia (DBP-DHP), and the detergent process was applied to bovine (DDBP)...
February 2018: Journal of Surgical Research
https://www.readbyqxmd.com/read/29243390/aquaporin-4-blockade-improves-survival-of-murine-heart-allografts-subjected-to-prolonged-cold-ischemia
#14
Katayoun Ayasoufi, Naoki Kohei, Michael Nicosia, Ran Fan, George W Farr, Paul R McGuirk, Marc F Pelletier, Robert L Fairchild, Anna Valujskikh
Prolonged cold ischemia storage (CIS) is a leading risk factor for poor transplant outcome. Existing strategies strive to minimize IRI in transplanted organs, yet there is a need for novel approaches to improve outcomes of marginal allografts and expand the pool of donor organs suitable for transplantation. Aquaporins (AQPs) are a family of water channels that facilitate homeostasis, tissue injury and inflammation. We tested whether inhibition of AQP4 improves the survival of fully MHC-mismatched murine cardiac allografts subjected to 8 h CIS...
December 15, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29233179/immature-morphological-properties-in-subcellular-scale-structures-in-the-dentate-gyrus-of-schnurri-2-knockout-mice-a-model-for-schizophrenia-and-intellectual-disability
#15
Akito Nakao, Naoyuki Miyazaki, Koji Ohira, Hideo Hagihara, Tsuyoshi Takagi, Nobuteru Usuda, Shunsuke Ishii, Kazuyoshi Murata, Tsuyoshi Miyakawa
Accumulating evidence suggests that subcellular-scale structures such as dendritic spine and mitochondria may be involved in the pathogenesis/pathophysiology of schizophrenia and intellectual disability. Previously, we proposed mice lacking Schnurri-2 (Shn2; also called major histocompatibility complex [MHC]-binding protein 2 [MBP-2], or human immunodeficiency virus type I enhancer binding protein 2 [HIVEP2]) as a schizophrenia and intellectual disability model with mild chronic inflammation. In the mutants' brains, there are increases in C4b and C1q genes, which are considered to mediate synapse elimination during postnatal development...
December 12, 2017: Molecular Brain
https://www.readbyqxmd.com/read/29229678/epitope-mapping-of-serca2a-identifies-an-antigenic-determinant-that-induces-mainly-atrial-myocarditis-in-a-j-mice
#16
Bharathi Krishnan, Chandirasegaran Massilamany, Rakesh H Basavalingappa, Arunakumar Gangaplara, Rajkumar A Rajasekaran, Muhammad Z Afzal, Vahid Khalilzad-Sharghi, You Zhou, Jean-Jack Riethoven, Shyam S Nandi, Paras K Mishra, Raymond A Sobel, Jennifer L Strande, David Steffen, Jay Reddy
Sarcoplasmic/endoplasmic reticulum Ca2+ adenosine triphosphatase (SERCA)2a, a critical regulator of calcium homeostasis, is known to be decreased in heart failure. Patients with myocarditis or dilated cardiomyopathy develop autoantibodies to SERCA2a suggesting that they may have pathogenetic significance. In this report, we describe epitope mapping analysis of SERCA2a in A/J mice that leads us to make five observations: 1) SERCA2a contains multiple T cell epitopes that induce varying degrees of myocarditis...
December 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29212956/icam1-neutrophils-promote-chronic-inflammation-via-asprv1-in-b-cell-dependent-autoimmune-encephalomyelitis
#17
Ryder F Whittaker Hawkins, Alexandre Patenaude, Aline Dumas, Rajiv Jain, Yodit Tesfagiorgis, Steven Kerfoot, Takeshi Matsui, Matthias Gunzer, Patrice E Poubelle, Catherine Larochelle, Martin Pelletier, Luc Vallières
Neutrophils contribute to demyelinating autoimmune diseases, yet their phenotype and functions have been elusive to date. Here, we demonstrate that ICAM1 surface expression distinguishes extra- from intravascular neutrophils in the mouse CNS during experimental autoimmune encephalomyelitis (EAE). Transcriptomic analysis of these 2 subpopulations indicated that neutrophils, once extravasated, acquire macrophage-like properties, including the potential for immunostimulation and MHC class II-mediated antigen presentation...
December 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/29212808/gestational-age-at-time-of-in-utero-lipopolysaccharide-exposure-influences-the-severity-of-inflammation-induced-diaphragm-weakness-in-lambs
#18
Kanakeswary Karisnan, Tanzila Mahzabin, Anthony J Bakker, Yong Song, Peter B Noble, J Jane Pillow, Gavin Jon Pinniger
The preterm diaphragm is functionally immature compared to its term counterpart. In utero inflammation further exacerbates preterm diaphragm dysfunction. We hypothesized that preterm lambs are more vulnerable to in utero inflammation induced diaphragm dysfunction compared with term lambs. Pregnant ewes received intra-amniotic (IA) injections of saline or 10mg lipopolysaccharide (LPS) 2d or 7d prior to delivery at 121d (preterm) or 145d (term) gestation. Diaphragm contractile function was assessed in vitro. Plasma cytokines and diaphragm myosin heavy chain (MHC) isoforms and oxidative stress were evaluated...
December 6, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29184496/andrographolide-protects-against-aortic-banding-induced-experimental-cardiac-hypertrophy-by-inhibiting-mapks-signaling
#19
Qing Q Wu, Jian Ni, Ning Zhang, Hai H Liao, Qi Z Tang, Wei Deng
Despite therapeutic advances, heart failure-related mortality rates remain high. Therefore, understanding the pathophysiological mechanisms involved in the remodeling process is crucial for the development of new therapeutic strategies. Andrographolide (Andr), a botanical compound, has potent cardio-protective effects due to its ability to inhibit mitogen-activated protein kinases (MAPKs). Andr has also been shown to inhibit inflammation and apoptosis, which are factors related to cardiac hypertrophy. Our aim was to evaluate the effects of Andr on cardiac hypertrophy and MAPKs activation...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29159903/soluble-mhc-molecules-in-immune-regulation-highlighting-class-ii-antigens
#20
REVIEW
Katerina Bakela, Irene Athanassakis
The involvement of Major histocompatibility complex (MHC) antigens in the development and regulation of immune response has been well defined over the years, starting from maturation, antigenic peptide loading, migration to the cell membrane for recognition by the T cell receptor and recycling for immune response cessation. During this intracellular trafficking, MHC antigens find a way to be excreted by the cells, since they can be found as soluble MHC class I (sMHCI) and class II (sMHCII) molecules in all body fluids...
November 21, 2017: Immunology
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