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MHC inflammation

Gil Benedek, Arthur A Vandenbark, Nabil J Alkayed, Halina Offner
The worldwide prevalence of stroke continues to rise despite recent successes in treating acute ischemic stroke. With limited patient eligibility and associated risk of tPA and mechanical thrombectomy, new preventive and therapeutic modalities are needed to stave the rising wave of stroke. Inflammation plays a key role in brain damage after cerebral ischemia, and novel therapies that target pro-inflammatory cells have demonstrated promise for treatment for stroke. Partial MHC class II constructs have been shown to prevent and/or reverse clinical signs of various inflammatory diseases such as experimental autoimmune encephalomyelitis, collagen-induced arthritis and experimental autoimmune uveitis, by reducing the number and frequency of activated cells in the damaged CNS...
October 20, 2016: Neurochemistry International
Huiting Su, Ning Na, Xiaodong Zhang, Yong Zhao
CD74 (MHC class II invariant chain, Ii) is a non-polymorphic type II transmembrane glycoprotein. It is clear that, in addition to be an MHC class II chaperone, CD74 has a diversity of biological functions in physiological and pathological situations. CD74 also participates in other non-MHC II protein trafficking, such as angiotensin II type I receptor. In addition, CD74 is a cell membrane high-affinity receptor for macrophage migration inhibitory factor (MIF), D-dopachrome tautomerase (D-DT/MIF-2) and bacterial proteins...
October 17, 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Kevin V Chow, Emma M Carrington, Yifan Zhan, Andrew M Lew, Robyn M Sutherland
Islet transplantation can cure type 1 diabetes, but is limited by lack of donor organs and early graft dysfunction, such that many patients require multiple transplants to achieve insulin independence. Monocyte derived dendritic cells (moDCs) arise during inflammation and allograft encounters where they can promote various innate and adaptive immune responses. To determine whether moDCs impair early graft function following allogeneic islet transplantation, we transplanted MHC-mismatched BALB/c (H-2d) islets into diabetic C57BL/6-CCR2...
October 13, 2016: Cell Transplantation
Andrew T Grainger, Michael B Jones, Jing Li, Mei-Hua Chen, Ani Manichaikul, Weibin Shi
BACKGROUND AND AIMS: Recent genome-wide association studies (GWAS) have identified over 50 significant loci containing common variants associated with coronary artery disease. However, these variants explain only 26% of the genetic heritability of the disease, suggesting that many more variants remain to be discovered. Here, we examined the genetic basis underlying the marked difference between SM/J-Apoe(-/-) and BALB/cJ-Apoe(-/-) mice in atherosclerotic lesion formation. METHODS: 206 female F2 mice generated from an intercross between the two Apoe(-/-) strains were fed 12 weeks of western diet...
October 6, 2016: Atherosclerosis
Carolyn M Kalsow, Steven S S T Ching, Ronald D Plotnik
PURPOSE: To investigate an immunopathogenesis of central and paracentral corneal ulceration associated with rheumatoid arthritis. METHODS: Sparse infiltrating cells in the ulcer area were identified by immunohistochemistry applied to archived formalin fixed, paraffin embedded tissues that had been recovered from patients undergoing penetrating keratoplasty necessitated by rheumatoid-associated central or paracentral corneal ulceration. RESULTS: Clinically, the ulcers presented as non-infiltrated lesions with a modicum of other ocular inflammation...
August 11, 2016: Ocular Immunology and Inflammation
James D H Ong, Ashley Mansell, Michelle D Tate
The severity of influenza A virus (IAV) infection can range from asymptotic to mild to severe. Infections, such as those seen following outbreaks of avian IAV, are associated with hyperinflammatory responses and the development of fatal disease. There is a continual threat that a novel or pandemic IAV will circulate in humans with high rates of mortality. The neuronal apoptosis inhibitor protein, class 2 transcription activator of the MHC, heterokaryon incompatibility, telomerase-associated protein 1, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome is an innate immune sensor that has been shown to be critical for the secretion of the potent proinflammatory cytokines, IL-1β and IL-18, as well as chemokine production and cellular inflammation in vivo following IAV infection...
October 5, 2016: Journal of Leukocyte Biology
Sachiko Tai, Jin-Yan Cheng, Hidee Ishii, Kasumi Shimono, Vincent Zangiacomi, Takatomo Satoh, Tetsuji Hosono, Emiko Suzuki, Ken Yamaguchi, Kouji Maruyama
Beta-tricalcium phosphate (β-TCP) is widely used for bone substitution in clinical practice. Particles of calcium phosphate ceramics including β-TCP act as an inflammation mediators, which is an unfavorable characteristic for a bone substituent or a prosthetic coating material. It is thought that the stimulatory effect of β-TCP on the immune system could be utilized as an immunomodulator. Here, in vitro effects of β-TCP on primary cultured murine dendritic cells (DCs) and macrophages were investigated. β-TCP particles enhanced expression of costimulatory surface molecules, including CD86, CD80, and CD40 in DCs, CD86 in macrophages, and MHC class II and class I molecules in DCs...
September 30, 2016: International Immunopharmacology
Stavroula Masouridi-Levrat, Federico Simonetta, Yves Chalandon
Bone marrow failure (BMF) syndromes are severe complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this paper, we distinguish two different entities, the graft failure (GF) and the poor graft function (PGF), and we review the current understanding of the interactions between the immune and hematopoietic compartments in these conditions. We first discuss how GF occurs as the result of classical alloreactive immune responses mediated by residual host cellular and humoral immunity persisting after conditioning and prevented by host and donor regulatory T cells...
2016: Frontiers in Immunology
Dasaradha Jalapothu, Margherita Boieri, Rachel E Crossland, Pranali Shah, Isha A Butt, Jean Norden, Ralf Dressel, Anne M Dickinson, Marit Inngjerdingen
MicroRNAs (miRNA) have emerged as central regulators of diverse biological processes and contribute to driving pathology in several diseases. Acute graft-versus-host disease (aGvHD) represents a major complication after allogeneic hematopoietic stem cell transplantation, caused by alloreactive donor T cells attacking host tissues leading to inflammation and tissue destruction. Changes in miRNA expression patterns occur during aGvHD, and we hypothesized that we could identify miRNA signatures in target tissues of aGvHD that may potentially help understand the underlying molecular pathology of the disease...
2016: Frontiers in Immunology
Kae Won Cho, Brian F Zamarron, Lindsey A Muir, Kanakadurga Singer, Cara E Porsche, Jennifer B DelProposto, Lynn Geletka, Kevin A Meyer, Robert W O'Rourke, Carey N Lumeng
Dynamic changes of adipose tissue leukocytes, including adipose tissue macrophage (ATM) and adipose tissue dendritic cells (ATDCs), contribute to obesity-induced inflammation and metabolic disease. However, clear discrimination between ATDC and ATM in adipose tissue has limited progress in the field of immunometabolism. In this study, we use CD64 to distinguish ATM and ATDC, and investigated the temporal and functional changes in these myeloid populations during obesity. Flow cytometry and immunostaining demonstrated that the definition of ATM as F4/80(+)CD11b(+) cells overlaps with other leukocytes and that CD45(+)CD64(+) is specific for ATM...
September 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Kristina Thamm, Florence Njau, Paul Van Slyke, Daniel J Dumont, Joon-Keun Park, Hermann Haller, Sascha David
AIM: To investigate the therapeutic potential of vasculotide (VT) - a Tie2 activating therapeutic - in kidney transplantation. METHODS: We performed a murine MHC-mismatched renal transplant model (C57Bl/6 male into Balb/c female) with 60 min cold and 30 min warm ischemia time. 500 ng VT was administered i.p. to donor mice 1 h before organ removal. In addition, recipients received 500 ng VT i.p. directly and 3 d after surgery. Survival was monitored and remaining animals were sacrificed 28 d after transplantation...
September 24, 2016: World Journal of Transplantation
Damian T Rieke, Sebastian Ochsenreither, Konrad Klinghammer, Tanguy Y Seiwert, Frederick Klauschen, Inge Tinhofer, Ulrich Keilholz
Immune checkpoints are emerging treatment targets, but mechanisms underlying checkpoint expression are poorly understood. Since alterations in DNA repair genes have been connected to the efficacy of checkpoint inhibitors, we investigated associations between methylation of DNA repair genes and CTLA4 and CD274 (PD-L1) expression.A list of DNA repair genes (179 genes) was selected from the literature, methylation status and expression of inflammation-associated genes (The Cancer Genome Atlas data) was correlated in head and neck squamous cell carcinoma (HNSCC), cervical and lung squamous cell carcinoma...
September 23, 2016: Oncotarget
Sharanya Prasad, Shelley R Starck, Nilabh Shastri
Cytolytic T cells eliminate infected or cancer cells by recognizing peptides presented by MHC class I molecules on the cell surface. The antigenic peptides are derived primarily from newly synthesized proteins including those produced by cryptic translation mechanisms. Previous studies have shown that cryptic translation can be initiated by distinct mechanisms at non-AUG codons in addition to conventional translation initiated at the canonical AUG start codon. In this study, we show that presentation of endogenously translated cryptic peptides is enhanced by TLR signaling pathways involved in pathogen recognition as well as by infection with different viruses...
September 19, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
W-J Cho, D-K Lee, S-Y Lee, S-H Sohn, H-L Park, Y-W Park, H Kim, J-H Nam
Obesity is a metabolic disease characterized by low-level chronic inflammation. Obese individuals are susceptible to infection by viruses, and vaccination against these pathogens is less effective than in nonobese individuals. Here, we sought to explore the immunological environment in a mouse model of obesity induced by a high-fat diet (HFD). HFD treatment increased the body weight and epididymal fat mass. The proportion of activated B cells, T cells, and macrophages was similar between mice in the HFD group and the regular-fat diet (RFD) group...
2016: Acta Virologica
Ming Xiang, Tingting Liu, Wanyue Tan, Hongyu Ren, Hua Li, Junjun Liu, Hui Cao, Qi Cheng, Xiulan Liu, Hucheng Zhu, Yali Tuo, Jianping Wang, Yonghui Zhang
: The central purpose of this study was to investigate therapeutic effects of the botanical derivative kinsenoside (KD) in experimental autoimmune hepatitis (AIH). Treatment with KD substantially reduced hepatic histopathological damage, induced by lymphocyte infiltration and pro-inflammatory cytokines, in ConA-induced T cell-mediated hepatitis, and in dendritic cells loaded with hepatocellular carcinoma cells (DC/Hepa1-6) induced murine AIH. Interactions between immune cells after KD treatment in AIH were detected by anti-CD8 antibody blocking, CD8(+) T cells sorting, and vaccinated mice with KD-pretreated DCs in a DC/Hepa1-6 model...
September 17, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Jiping Zhao, Hao Yu, Yudong Liu, Sara A Gibson, Zhaoqi Yan, Xin Xu, Amit Gaggar, Pui-Kai Li, Chenglong Li, Shi Wei, Etty N Benveniste, Hongwei Qin
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are diseases with high mortality. Macrophages and neutrophils are responsible for inflammatory responses in ALI and ARDS, which are characterized by excessive production of proinflammatory mediators in bronchoalveolar lavage fluid (BALF) and plasma. Aberrant activation of the JAK/STAT pathway is critical for persistent inflammation in many conditions such as infection and autoimmunity. Given the importance of the STAT3 transcription factor in activating macrophages and neutrophils, and augmenting inflammation, we investigated the therapeutic potential of inhibiting STAT3 activity using the small molecule STAT3 inhibitor, LLL12...
September 16, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Kristina Berg Lorvik, Clara Hammarstrom, Marte Fauskanger, Ole Audun Werner Haabeth, Michael Zangani, Guttorm Haraldsen, Bjarne Bogen, Alexandre Corthay
Adoptive cell therapy (ACT) trials to date have focused on transfer of autologous tumor-specific cytotoxic CD8+ T cells, however, the potential of CD4+ T helper (Th) cells for ACT is gaining interest. While encouraging results have been reported with interferon-γ (IFNγ)-producing Th1 cells, tumor-specific Th2 cells have been largely neglected for ACT due to their reported tumor-promoting properties. In this study, we tested the efficacy of idiotype-specific Th2 cells for the treatment of mice with Major Histocompatibility Complex (MHC) class II-negative myeloma...
September 12, 2016: Cancer Research
Dallas Jones, Anna Blackmon, C Preston Neff, Brent E Palmer, Don Gilden, Hussain Badani, Maria A Nagel
: Varicella zoster virus (VZV) vasculopathy produces stroke, giant cell arteritis and granulomatous aortitis and develops after virus reactivates from ganglia and spreads transaxonally to arterial adventitia, resulting in persistent inflammation and pathological vascular remodeling. The mechanism(s) by which inflammatory cells persist in VZV-infected arteries is unknown; however, virus-induced dysregulation of programmed death ligand 1 (PD-L1) may play a role. Specifically, PD-L1 is expressed on virtually all nucleated cells and suppresses the immune system by interacting with the programmed cell death protein receptor 1 found exclusively on immune cells; thus, downregulation of PD-L1 may promote inflammation as seen in some autoimmune diseases...
September 14, 2016: Journal of Virology
Raphaël Bernard-Valnet, Lidia Yshii, Clémence Quériault, Xuan-Hung Nguyen, Sébastien Arthaud, Magda Rodrigues, Astrid Canivet, Anne-Laure Morel, Arthur Matthys, Jan Bauer, Béatrice Pignolet, Yves Dauvilliers, Christelle Peyron, Roland S Liblau
Narcolepsy with cataplexy is a rare and severe sleep disorder caused by the destruction of orexinergic neurons in the lateral hypothalamus. The genetic and environmental factors associated with narcolepsy, together with serologic data, collectively point to an autoimmune origin. The current animal models of narcolepsy, based on either disruption of the orexinergic neurotransmission or neurons, do not allow study of the potential autoimmune etiology. Here, we sought to generate a mouse model that allows deciphering of the immune mechanisms leading to orexin(+) neuron loss and narcolepsy development...
September 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
Tomica Ambang, Joo-San Tan, Sheila Ong, Kum-Thong Wong, Khean-Jin Goh
Telbivudine, a thymidine nucleoside analog, is a common therapeutic option for chronic hepatitis B infection. While raised serum creatine kinase is common, myopathy associated with telbivudine is rare. Reports on its myopathological features are few and immunohistochemical analyses of inflammatory cell infiltrates have not been previously described. We describe the clinical, myopathological and immunohistochemical features of four patients who developed myopathy after telbivudine therapy for chronic hepatitis B infection...
2016: PloS One
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