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https://www.readbyqxmd.com/read/27915019/the-impact-of-cell-surface-pegylation-and-short-course-immunotherapy-on-islet-graft-survival-in-an-allogeneic-murine-model
#1
Jaime A Giraldo, R Damaris Molano, Hernán R Rengifo, Carmen Fotino, Kerim M Gattás-Asfura, Antonello Pileggi, Cherie L Stabler
: Islet transplantation is a promising therapy for Type 1 diabetes mellitus; however, host inflammatory and immune responses lead to islet dysfunction and destruction, despite potent systemic immunosuppression. Grafting of poly(ethylene glycol) (PEG) to the periphery of cells or tissues can mitigate inflammation and immune recognition via generation of a steric barrier. Herein, we sought to evaluate the complementary impact of islet PEGylation with a short-course immunotherapy on the survival of fully-MHC mismatched islet allografts (DBA/2 islets into diabetic C57BL/6J recipients)...
November 30, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27908893/tracking-monocyte-recruitment-and-macrophage-accumulation-in-atherosclerotic-plaque-progression-using-a-novel-hcd68gfp-apoe-reporter-mouse
#2
Eileen McNeill, Asif J Iqbal, Daniel Jones, Jyoti Patel, Patricia Coutinho, Lewis Taylor, David R Greaves, Keith M Channon
OBJECTIVE: To create a model of atherosclerosis using green fluorescent protein (GFP)-targeted monocytes/macrophages, allowing analysis of both endogenous GFP(+) and adoptively transferred GFP(+) myeloid cells in arterial inflammation. APPROACH AND RESULTS: hCD68GFP reporter mice were crossed with ApoE(-/-) mice. Expression of GFP was localized to macrophages in atherosclerotic plaques and in angiotensin II-induced aortic aneurysms and correlated with galectin 3 and mCD68 expression. Flow cytometry confirmed GFP(+) expression in CD11b(+)/CD64(+), CD11c(+)/MHC-II(HI), and CD11b(+)/F4/80(+) myeloid cells...
December 1, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27907087/prenylated-polyphenols-from-clusiaceae-and-calophyllaceae-with-immunomodulatory-activity-on-endothelial-cells
#3
Caroline Rouger, Sylvain Pagie, Séverine Derbré, Anne-Marie Le Ray, Pascal Richomme, Béatrice Charreau
Endothelial cells (ECs) are key players in inflammation and immune responses involved in numerous pathologies. Although attempts were experimentally undertaken to prevent and control EC activation, drug leads and probes still remain necessary. Natural products (NPs) from Clusiaceous and Calophyllaceous plants were previously reported as potential candidates to prevent endothelial dysfunction. The present study aimed to identify more precisely the molecular scaffolds that could limit EC activation. Here, 13 polyphenols belonging to 5 different chemical types of secondary metabolites (i...
2016: PloS One
https://www.readbyqxmd.com/read/27861817/a-novel-spontaneous-mutation-in-the-tap2-gene-unravels-its-role-in-macrophage-survival
#4
Antonio Lapenna, Ibrahim Omar, Michael Berger
Here we report a new mouse strain with a single point mutation in the type 2 transporter associated with antigen processing (TAP2). This strain randomly arose in one of our C57BL/6J mouse colony and was initially discovered due to lack of CD8(+) T cells in the periphery. Following our observation, we subsequently revealed a lack of cell surface major histocompatibility complex (MHC-I) expression, derived from TAP2 protein deficiency. Our strain, named eightless, has a C to T substitution in exon 5 resulting in a glutamine to stop codon substitution at position 285 in the TAP2 protein...
November 18, 2016: Immunology
https://www.readbyqxmd.com/read/27837111/age-associated-b-cells-with-proinflammatory-characteristics-are-expanded-in-a-proportion-of-multiple-sclerosis-patients
#5
Nele Claes, Judith Fraussen, Marjan Vanheusden, Niels Hellings, Piet Stinissen, Bart Van Wijmeersch, Raymond Hupperts, Veerle Somers
Immune aging occurs in the elderly and in autoimmune diseases. Recently, IgD(-)CD27(-) (double negative, DN) and CD21(-)CD11c(+) (CD21(low)) B cells were described as age-associated B cells with proinflammatory characteristics. This study investigated the prevalence and functional characteristics of DN and CD21(low) B cells in multiple sclerosis (MS) patients. Using flow cytometry, we demonstrated a higher proportion of MS patients younger than 60 y with peripheral expansions of DN (8/41) and CD21(low) (9/41) B cells compared with age-matched healthy donors (1/33 and 2/33, respectively), which indicates an increase in age-associated B cells in MS patients...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27816788/tlr4-hmgb1-signaling-pathway-affects-the-inflammatory-reaction-of-autoimmune-myositis-by-regulating-mhc-i
#6
Zemin Wan, Xiujuan Zhang, Anping Peng, Min He, Zhenhua Lei, Yunxiu Wang
OBJECTIVES: To analyze the effects of TLR4 on the expression of the HMGB1, MHC-I and downstream cytokines IL-6 and TNF-α, and to investigate the biological role of the TLR4-HMGB1 signaling pathway in the development of the autoimmune myositis. METHODS: We built mice models with experimental autoimmune myositis (EAM) and used the inverted screen experiment to measure their muscle endurance; we also examined inflammatory infiltration of muscle tissues after HE staining; and we assessed the expression of MHC-I using immunohistochemistry...
November 3, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27815446/blood-stem-cell-activity-is-arrested-by-th1-mediated-injury-preventing-engraftment-following-nonmyeloablative-conditioning
#7
Antonia M S Müller, Mareike Florek, Holbrook E K Kohrt, Natascha J Küpper, Alexander Filatenkov, Jessica A Linderman, Husein Hadeiba, Robert S Negrin, Judith A Shizuru
T cells are widely used to promote engraftment of hematopoietic stem cells (HSCs) during an allogeneic hematopoietic cell transplantation. Their role in overcoming barriers to HSC engraftment is thought to be particularly critical when patients receive reduced doses of preparative chemotherapy and/or radiation compared with standard transplantations. In this study, we sought to delineate the effects CD4(+) cells on engraftment and blood formation in a model that simulates clinical hematopoietic cell transplantation by transplanting MHC-matched, minor histocompatibility-mismatched grafts composed of purified HSCs, HSCs plus bulk T cells, or HSCs plus T cell subsets into mice conditioned with low-dose irradiation...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27806341/exogenous-cathepsin-g-upregulates-cell-surface-mhc-class-i-molecules-on-immune-and-glioblastoma-cells
#8
Madleen Giese, Nadine Turiello, Nicole Molenda, David Palesch, Annika Meid, Roman Schroeder, Paola Basilico, Charaf Benarafa, Marc-Eric Halatsch, Michal Zimecki, Mike-Andrew Westhoff, Christian Rainer Wirtz, Timo Burster
Major histocompatibility complex (MHC) class I molecules present antigenic peptides to cytotoxic T cells. During an adaptive immune response, MHC molecules are regulated by several mechanisms including lipopolysaccharide (LPS) and interferon gamma (IFN-g). However, it is unclear whether the serine protease cathepsin G (CatG), which is generally secreted by neutrophils at the site of inflammation, might regulate MHC I molecules. We identified CatG, and to a higher extend CatG and lactoferrin (LF), as an exogenous regulator of cell surface MHC I expression of immune cells and glioblastoma stem cells...
October 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27799310/cd8%C3%AE-%C3%AE-mhc-class-ii-cell-with-the-capacity-to-terminate-autoimmune-inflammation-is-a-novel-antigen-presenting-nk-like-cell-in-rats
#9
Jean Wu, Colin Carlock, April Ross, Junbo Shim, Yahuan Lou
Discovery of immune tolerance mechanisms, which inhibit pre-existing autoimmune inflammation, may provide us with new strategies for treating autoimmune diseases. We have identified a CD8αα(+)MHC class II(+) cell with professional APC capacity during our investigation on spontaneous recovery from autoimmune glomerulonephritis in a rat model. This cell actively invades inflamed target tissue and further terminates an ongoing autoimmune inflammation by selective killing of effector autoreactive T cells. In this study, we show that this cell used a cytotoxic machinery of Ly49s(+) NK cells in killing of target T cells...
December 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27793007/elevation-of-c-reactive-protein-levels-in-patients-with-transfusion-related-acute-lung-injury
#10
Rick Kapur, Michael Kim, Matthew T Rondina, Leendert Porcelijn, John W Semple
Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related fatalities and is characterized by the onset of acute respiratory distress within six hours following blood transfusion. In most cases, donor antibodies are suggested to be involved, however, the pathogenesis is poorly understood. A two-hit model is generally assumed to underlie TRALI pathogenesis where the first hit consists of a patient predisposing factor such as inflammation and the second hit is due to donor antibodies present in the transfused blood...
October 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27783202/protective-and-pathogenic-roles-of-cd8-t-cells-in-atherosclerosis
#11
REVIEW
Clement Cochain, Alma Zernecke
Although infiltration of CD8(+) T cells in human atherosclerotic lesions has been described 30 years ago, the role of these cells in lesion development has long remained enigmatic. While experimental models hinted at their pro-atherogenic role based on circumstantial evidence, genetic mouse models of cytotoxic CD8(+) T cell-specific immune deficiency suggested no crucial role of these cells in lesion development. However, in recent years, more refined models of adoptive cell transfer, disruption of specific immune regulatory pathways or monoclonal antibody-mediated cell depletion have proposed both atheroprotective and pro-atherogenic functions for CD8(+) T cells in atherosclerosis...
November 2016: Basic Research in Cardiology
https://www.readbyqxmd.com/read/27773790/partial-mhc-class-ii-constructs-as-novel-immunomodulatory-therapy-for-stroke
#12
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 31, 2016: Neurochemistry International
https://www.readbyqxmd.com/read/27752708/the-biological-function-and-significance-of-cd74-in-immune-diseases
#13
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.]
https://www.readbyqxmd.com/read/27743446/monocyte-derived-dendritic-cells-impair-early-graft-function-following-allogeneic-islet-transplantation
#14
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
https://www.readbyqxmd.com/read/27736672/genetic-analysis-of-atherosclerosis-identifies-a-major-susceptibility-locus-in-the-major-histocompatibility-complex-of-mice
#15
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
https://www.readbyqxmd.com/read/27715362/cellular-infiltrate-in-rheumatoid-arthritis-associated-paracentral-corneal-ulceration
#16
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
https://www.readbyqxmd.com/read/27707881/hero-turned-villain-nlrp3-inflammasome-induced-inflammation-during-influenza-a-virus-infection
#17
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
https://www.readbyqxmd.com/read/27697725/effects-of-beta-tricalcium-phosphate-particles-on-primary-cultured-murine-dendritic-cells-and-macrophages
#18
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
https://www.readbyqxmd.com/read/27695456/immunological-basis-of-bone-marrow-failure-after-allogeneic-hematopoietic-stem-cell-transplantation
#19
REVIEW
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
https://www.readbyqxmd.com/read/27695455/tissue-specific-expression-patterns-of-microrna-during-acute-graft-versus-host-disease-in-the-rat
#20
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
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