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Dendritic cell and arthritis

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https://www.readbyqxmd.com/read/28401953/overexpression-of-heparanase-enhances-t-lymphocyte-activities-and-intensifies-the-inflammatory-response-in-a-model-of-murine-rheumatoid-arthritis
#1
Andreas Digre, Kailash Singh, Magnus Åbrink, Rogier M Reijmers, Stellan Sandler, Israel Vlodavsky, Jin-Ping Li
Heparanase is an endo-glucuronidase that degrades heparan sulfate chains. The enzyme is expressed at a low level in normal organs; however, elevated expression of heparanase has been detected in several inflammatory conditions, e.g. in the synovial joints of rheumatoid arthritis (RA) patients. Herein, we have applied the model of collagen-induced arthritis (CIA) to transgenic mice overexpressing human heparanase (Hpa-tg) along with wildtype (WT) mice. About 50% of the induced animals developed clinical symptoms, i...
April 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28376277/dendritic-cells-from-rheumatoid-arthritis-patient-peripheral-blood-induce-th17-cell-differentiation-via-mir-363-integrin-%C3%AE-v-tgf-%C3%AE-axis
#2
Feng Pan, Haiyan Xiang, Juzhen Yan, Liquan Hong, Lahong Zhang, Yuhua Liu, Xiao Feng, Chengsong Cai
BACKGROUND AND AIM: Dendritic cells (DCs) are critical regulators of immune responses. This study was to observe the effect of DCs from peripheral blood on the differentiation of Th17 in rheumatoid arthritis (RA) patients. METHODS AND RESULTS: Peripheral blood samples were collected from 30 RA patients and 20 healthy controls, respectively. Flow cytometry results showed that in contrast with Treg cells, the proportion of Th17 cells in T cells and the Th17/Treg ratio were both increased in RA patients...
April 4, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28371836/differential-effects-of-biological-dmards-on-peripheral-immune-cell-phenotypes-in-patients-with-rheumatoid-arthritis
#3
Shingo Nakayamada, Satoshi Kubo, Maiko Yoshikawa, Yusuke Miyazaki, Naoki Yunoue, Shigeru Iwata, Ippei Miyagawa, Shintaro Hirata, Kazuhisa Nakano, Kazuyoshi Saito, Yoshiya Tanaka
Objective.: The aim of this study was to assess the therapeutic effects of biological DMARDs (bDMARDs) on the diversity of immune cell phenotypes in peripheral blood of patients with RA. Methods.: Peripheral immune cell phenotypes were determined in 108 RA patients who were non-responsive to conventional DMARDs and 33 healthy control subjects by eight-colour flow cytometry. We also examined the correlation between the phenotypes and clinical findings and assessed the effects of 24-week treatment with bDMARDs...
March 27, 2017: Rheumatology
https://www.readbyqxmd.com/read/28357074/traf6-regulates-the-effects-of-polarized-maturation-of-tolerability-marrow-derived-dendritic-cells-on-collagen-induced-arthritis-in-mice
#4
Chenchen Zhuang, Xuezhi Hong, Jia Liu, Xiaohong Luo, Hanyou Mo
The study aimed to investigate the relationship between tumor necrosis factor receptor-associated factor 6 (TRAF6) and a differentially mature dendritic cell (mDC) in collagen-induced arthritis (CIA) mice and to determine whether or not TRAF6 regulates the activation of an immature dendritic cell (iDC) and inhibits iDC maturation to induce immune tolerance. The mouse bone marrow stem cells were induced with recombinant granulocyte-macrophage colony-stimulating factor (rmGM-CSF) and recombinant interleukin-4 (rmIL-4) to differentiate immature dendritic cells (DCs), which were divided into four groups with different maturation states: rmGM-CSF, rmIL-4; TNF-α; LPS; and FK506 group...
February 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28274252/elevated-serum-autoantibodies-against-co-inhibitory-pd-1-facilitate-t-cell-proliferation-and-correlate-with-disease-activity-in-new-onset-systemic-lupus-erythematosus-patients
#5
Hui Shi, Junna Ye, Jialin Teng, Yufeng Yin, Qiongyi Hu, Xinyao Wu, Honglei Liu, Xiaobing Cheng, Yutong Su, Mengru Liu, Juanfang Gu, Ting Lu, HaoJie Chen, Hui Zheng, Yue Sun, Chengde Yang
BACKGROUND: Programmed cell death protein 1 (PD-1) plays an important role in immune response regulation as a co-inhibitory signal during T cell activation. However, there is little known about the serum autoantibody profile of PD-1 in systemic lupus erythematosus (SLE), a disease characterized by the breakdown of immune tolerance to self-antigens and an excessive production of autoantibodies. Thus, we aim to investigate the serum levels and function of anti-PD-1 in patients with new-onset SLE...
March 9, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28267648/expression-of-soluble-cd83-in-plasma-from-early-stage-rheumatoid-arthritis-patients-is-not-modified-by-anti-tnf-%C3%AE-therapy
#6
Anne-Mette Kristensen, Kristian Stengaard-Pedersen, Merete Lund Hetland, Kim Hørslev-Petersen, Peter Junker, Mikkel Østergaard, Per Höllsberg, Bent Deleuran, Malene Hvid
Rheumatoid arthritis (RA) is an autoimmune disease which may lead to severe disabilities due to structural joint damage and extraarticular manifestations The dendritic cell marker CD83 belongs to the immunoglobulin superfamily and has previously been associated with autoimmune diseases. In RA the levels of soluble CD83 (sCD83) are elevated in synovial fluid, however little is known about CD83 expression and regulation in RA. Therefore, we studied how CD83 is expressed in RA and further evaluated the effect of anti-TNF-α therapy hereon...
March 3, 2017: Cytokine
https://www.readbyqxmd.com/read/28237724/the-common-autoimmunity-predisposing-620arg%C3%A2-%C3%A2-trp-variant-of-ptpn22-modulates-macrophage-function-and-morphology
#7
Meihang Li, Hugues Beauchemin, Natalija Popovic, Alan Peterson, Eva d'Hennezel, Ciriaco A Piccirillo, Chao Sun, Constantin Polychronakos
The C1858T single nucleotide polymorphism (SNP) in PTPN22 (protein tyrosine phosphatase nonreceptor 22) leads to the 620 Arg to Trp polymorphism in its encoded human protein LYP. This allelic variant is associated with multiple autoimmune diseases, including type 1 diabetes (T1D), Crohn's disease, rheumatoid arthritis and systemic lupus erythematosus. However, the underlying mechanisms are poorly understood. To study how this polymorphism influences the immune system, we generated a mouse strain with a knock-in of the Trp allele, imitating the human disease-associated variant...
February 22, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28236220/the-function-of-myeloid-dendritic-cells-in-rheumatoid-arthritis
#8
REVIEW
Mary Beth Yu, William H R Langridge
Rheumatoid arthritis (RA) is a systemic autoimmune disease that causes joint pain, inflammation, and loss of function. Disease pathogenesis involves activation and proliferation of autoreactive pro-inflammatory effector T cells. While the details of RA onset and progression remain controversial, dendritic cell (DC) numbers dramatically increase in the synovial joint tissues of RA patients. Based on their key functions as antigen-presenting cells and inducers of T cell differentiation, DCs may play an important role in the initiation of joint inflammation...
February 24, 2017: Rheumatology International
https://www.readbyqxmd.com/read/28230210/synergistic-suppression-of-autoimmune-arthritis-through-concurrent-treatment-with-tolerogenic-dc-and-msc
#9
Rong Li, Yujuan Zhang, Xiufen Zheng, Shanshan Peng, Keng Yuan, Xusheng Zhang, Weiping Min
Rheumatoid arthritis (RA) is an autoimmune disease characterized by progressive immune-mediated joint deterioration. Current treatments are not antigen specific and are associated with various adverse. We have previously demonstrated that tolerogenic dendritic cells (Tol-DC) are potent antigen-specific immune regulators, which hold great promise in immunotherapy of autoimmune diseases. In this study, we aimed to develop new immunotherapy by combining Tol-DC and mesenchymal stem cells (MSC). We demonstrated that RelB gene silencing resulted in generation of Tol-DC that suppressed T cell responses and selectively promoted Treg generation...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28216098/potential-influences-of-complement-factor-h-in-autoimmune-inflammatory-and-thrombotic-disorders
#10
Janez Ferluga, Lubna Kouser, Valarmathy Murugaiah, Robert B Sim, Uday Kishore
Complement system homeostasis is important for host self-protection and anti-microbial immune surveillance, and recent research indicates roles in tissue development and remodelling. Complement also appears to have several points of interaction with the blood coagulation system. Deficiency and altered function due to gene mutations and polymorphisms in complement effectors and regulators, including Factor H, have been associated with familial and sporadic autoimmune inflammatory - thrombotic disorders, in which autoantibodies play a part...
April 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28201972/cell-based-tolerogenic-therapy-experience-from-animal-models-of-multiple-sclerosis-type-1-diabetes-and-rheumatoid-arthritis
#11
Ivana Stojanović, Mirjana Dimitrijević, Marta Vives-Pi, Maria Jose Mansilla, Irma Pujol-Autonell, Silvia Rodríguez-Fernandez, Lenka Palová-Jelínková, David P Funda, Alisa Gruden-Movsesijan, Ljiljana Sofronić-Milosavljević, Catharien M U Hilkens, Eva Martínez-Cáceres, Djordje Miljković
Cell-based tolerogenic therapy is a promising approach for the treatment of autoimmune diseases and transplant rejection. Regulatory T cells and tolerogenic dendritic cells have been particularly explored in the treatment of various autoimmune disorders in experimental models of disease. Although some of these cells have already been tested in a limited number of clinical trials, there is still a need for preclinical research on tolerogenic cells in animal models of autoimmunity. This review will focus on the relevance of data obtained from studies in experimental animal models for the use of tolerogenic cell-based therapy in humans...
February 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28191643/cd11b-regulates-the-treg-th17-balance-in-murine-arthritis-via-il-6
#12
Mathias Stevanin, Nathalie Busso, Véronique Chobaz, Matteo Pigni, Sahar Ghassem-Zadeh, Li Zhang, Hans Acha-Orbea, Driss Ehirchiou
Th17 cells are often associated with autoimmunity and been shown to be increased in CD11b(-/-) mice. Here, we examined the role of CD11b in murine collagen-induced arthritis (CIA). C57BL/6 and CD11b(-/-) resistant mice were immunized with type II collagen. CD11b(-/-) mice developed arthritis with early onset, high incidence, and sustained severity compared with C57BL/6 mice. We observed a marked leukocyte infiltration, and histological examinations of the arthritic paws from CD11b(-/-) mice revealed that the cartilage was destroyed in association with strong lymphocytic infiltration...
February 12, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28186160/3-bromopyruvate-ameliorate-autoimmune-arthritis-by-modulating-th17-treg-cell-differentiation-and-suppressing-dendritic-cell-activation
#13
Takaichi Okano, Jun Saegusa, Keisuke Nishimura, Soshi Takahashi, Sho Sendo, Yo Ueda, Akio Morinobu
Recent studies have shown that cellular metabolism plays an important role in regulating immune cell functions. In immune cell differentiation, both interleukin-17-producing T (Th17) cells and dendritic cells (DCs) exhibit increased glycolysis through the upregulation of glycolytic enzymes, such as hexokinase-2 (HK2). Blocking glycolysis with 2-deoxyglucose was recently shown to inhibit Th17 cell differentiation while promoting regulatory T (Treg) cell generation. However, 2-DG inhibits all isoforms of HK. Thus, it is unclear which isoform has a critical role in Th17 cell differentiation and in rheumatoid arthritis (RA) pathogenesis...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28165033/micheliolide-provides-protection-of-mice-against-staphylococcus-aureus-and-mrsa-infection-by-down-regulating-inflammatory-response
#14
Xinru Jiang, Yuli Wang, Yifei Qin, Weigang He, Adel Benlahrech, Qingwen Zhang, Xin Jiang, Zhenhui Lu, Guang Ji, Yuejuan Zheng
A major obstacle to therapy in intensive care units is sepsis caused by severe infection. In recent years gram-positive (G(+)) bacteria, most commonly staphylococci, are thought to be the main pathogens. Micheliolide (MCL) was demonstrated to provide a therapeutic role in rheumatoid arthritis, inflammatory intestinal disease, colitis-associated cancer, and lipopolysaccharide (LPS, the main component of G(-) bacterial cell wall) induced septic shock. We proved here that MCL played an anti-inflammatory role in Staphylococcus aureus (S...
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28130494/oxidized-low-density-lipoprotein-immune-complex-priming-of-the-nlrp3-inflammasome-involves-tlr-and-fc%C3%AE-r-cooperation-and-is-dependent-on-card9
#15
Jillian P Rhoads, John R Lukens, Ashley J Wilhelm, Jared L Moore, Yanice Mendez-Fernandez, Thirumala-Devi Kanneganti, Amy S Major
Oxidized low-density lipoprotein (oxLDL) is known to activate inflammatory responses in a variety of cells, especially macrophages and dendritic cells. Interestingly, much of the oxLDL in circulation is complexed to Abs, and these resulting immune complexes (ICs) are a prominent feature of chronic inflammatory disease, such as atherosclerosis, type-2 diabetes, systemic lupus erythematosus, and rheumatoid arthritis. Levels of oxLDL ICs often correlate with disease severity, and studies demonstrated that oxLDL ICs elicit potent inflammatory responses in macrophages...
March 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28127756/absence-of-dcir1-reduces-the-mortality-rate-of-endotoxemic-hepatitis-in-mice
#16
Toshifumi Ishiguro, Tetsuya Fukawa, Kotaro Akaki, Koji Nagaoka, Tatsuki Takeda, Yoichiro Iwakura, Kayo Inaba, Kazuhiko Takahara
Dendritic cell immunoreceptor (DCIR) is a C-type lectin with an immunoreceptor tyrosine-based inhibitory motif (ITIM). Mice lacking DCIR1 (Dcir1(-/-) mice) show higher susceptibility to chronic arthritis with increasing age, suggesting that DCIR1 is involved in immune modulation via its ITIM. However, the role of DCIR1 in acute immune responses is not clear. In this study, we explored its role in acute experimental hepatitis. Upon injection of d-galactosamine and lipopolysaccharide, Dcir1(-/-) mice showed decreased mortality rates and serum levels of alanine aminotransferase...
January 26, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28100093/p19-targeted-abd-derived-protein-variants-inhibit-il-23-binding-and-exert-suppressive-control-over-il-23-stimulated-expansion-of-primary-human-il-17-t-cells
#17
Lucie Křížová, Milan Kuchař, Hana Petroková, Radim Osička, Marie Hlavničková, Ondřej Pelák, Jiří Černý, Tomáš Kalina, Petr Malý
Interleukin-23 (IL-23), a heterodimeric cytokine of covalently bound p19 and p40 proteins, has recently been closely associated with development of several chronic autoimmune diseases such as psoriasis, psoriatic arthritis or inflammatory bowel disease. Released by activated dendritic cells, IL-23 interacts with IL-23 receptor (IL-23R) on Th17 cells, thus promoting intracellular signaling, a pivotal step in Th17-driven pro-inflammatory axis. Here, we aimed to block the binding of IL-23 cytokine to its cell-surface receptor by novel inhibitory protein binders targeted to the p19 subunit of human IL-23...
January 19, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28063059/experimental-arthritis-mouse-models-driven-by-adaptive-and-or-innate-inflammation
#18
W Razawy, C H Alves, M Molendijk, P S Asmawidjaja, A M C Mus, E Lubberts
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease mainly affecting synovial joints. The clinical presentation of RA shows the heterogeneity of this disease with its underlying complex interactions between the innate and adaptive immune system and flare-ups of disease. Different disease models such as collagen induced arthritis, antigen induced arthritis, and Streptococcal cell wall induced arthritis can be exploited to investigate different aspects of the pathogenesis of arthritis. The disease can be monitored macroscopically over time via scoring systems...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27959965/functional-analyses-of-the-crohn-s-disease-risk-gene-lacc1
#19
Ghazaleh Assadi, Liselotte Vesterlund, Ferdinando Bonfiglio, Luca Mazzurana, Lina Cordeddu, Danika Schepis, Jenny Mjösberg, Sabrina Ruhrmann, Alessia Fabbri, Vladana Vukojevic, Piergiorgio Percipalle, Florian A Salomons, Jurga Laurencikiene, Leif Törkvist, Jonas Halfvarson, Mauro D'Amato
BACKGROUND: Genetic variation in the Laccase (multicopper oxidoreductase) domain-containing 1 (LACC1) gene has been shown to affect the risk of Crohn's disease, leprosy and, more recently, ulcerative colitis and juvenile idiopathic arthritis. LACC1 function appears to promote fatty-acid oxidation, with concomitant inflammasome activation, reactive oxygen species production, and anti-bacterial responses in macrophages. We sought to contribute to elucidating LACC1 biological function by extensive characterization of its expression in human tissues and cells, and through preliminary analyses of the regulatory mechanisms driving such expression...
2016: PloS One
https://www.readbyqxmd.com/read/27941390/mesenchymal-stem-cells-for-the-management-of-rheumatoid-arthritis-immune-modulation-repair-or-both
#20
Sharon Ansboro, Anke J Roelofs, Cosimo De Bari
PURPOSE OF REVIEW: Mesenchymal stromal/stem cells (MSCs) have potent anti-inflammatory and immunomodulatory properties, in addition to their ability to form cartilage and bone. The purpose of this review is to highlight recent developments and current knowledge gaps in our understanding of the protective effects of MSCs against inflammatory arthritis, and to discuss their clinical exploitation for the treatment of rheumatoid arthritis (RA). RECENT FINDINGS: The weight of evidence for protective mechanisms of exogenously administered MSCs is on immunomodulatory effects, including inhibition of dendritic cell maturation, polarization of macrophages to an anti-inflammatory phenotype, and activation of regulatory T cells, thereby dampening inflammation and preventing joint damage...
March 2017: Current Opinion in Rheumatology
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