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Dendritic cell and arthritis

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https://www.readbyqxmd.com/read/28230210/synergistic-suppression-of-autoimmune-arthritis-through-concurrent-treatment-with-tolerogenic-dc-and-msc
#1
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
#2
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...
February 16, 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
#3
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...
14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28191643/cd11b-regulates-via-il-6-the-treg-th17-balance-in-murine-arthritis
#4
Mathias Stevanin, Nathalie Busso, Veronique 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)-induced arthritis. 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
#5
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
#6
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
#7
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
#8
Toshifumi Ishiguro, Testuya 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 (ALT)...
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/27931982/jak-inhibitor-tofacitinib-suppresses-interferon-alfa-production-by-plasmacytoid-dendritic-cells-and-inhibits-arthrogenic-and-antiviral-effects-of-interferon-alfa
#13
Patrick P C Boor, Petra E de Ruiter, Patrick S Asmawidjaja, Erik Lubberts, Luc J W van der Laan, Jaap Kwekkeboom
Tofacitinib is an oral Janus kinase inhibitor that is effective for the treatment of rheumatoid arthritis and shows encouraging therapeutic effects in several other autoimmune diseases. A prominent adverse effect of tofacitinib therapy is the increased risk of viral infections. Despite its advanced stage of clinical development, the modes of action that mediate the beneficial and adverse effects of tofacitinib in autoimmune diseases remain unclear. Interferon alfa (IFNα) produced by plasmacytoid dendritic cells (PDCs) is critically involved in the pathogenesis of many systemic autoimmune diseases and in immunity to viral infections...
November 20, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27913299/the-inhibitory-effect-of-beta-lapachone-on-rankl-induced-osteoclastogenesis
#14
Dong Ryun Gu, Joon No Lee, Gi-Su Oh, Hyung Jin Kim, Min Seuk Kim, Seoung Hoon Lee
β-lapachone (β-L) is a substrate of reduced nicotinamide adenine dinucleotide (NADH): quinone oxidoreductase 1 (NQO1). NQO1 reduces quinones to hydroquinones using NADH as an electron donor and consequently increases the intracellular NAD+/NADH ratio. The activation of NQO1 by β-L has beneficial effects on several metabolic syndromes, such as obesity, hypertension, and renal injury. However, the effect of β-L on bone metabolism remains unclear. Here, we show that β-L might be a potent inhibitor of receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27908288/granulocyte-macrophage-colony-stimulating-factor-receptor-%C3%AE-expression-and-its-targeting-in-antigen-induced-arthritis-and-inflammation
#15
Andrew D Cook, Cynthia Louis, Matthew J Robinson, Reem Saleh, Matthew A Sleeman, John A Hamilton
BACKGROUND: Blockade of granulocyte macrophage colony-stimulating factor (GM-CSF) and its receptor (GM-CSFRα) is being successfully tested in trials in rheumatoid arthritis (RA) with clinical results equivalent to those found with neutralization of the current therapeutic targets, TNF and IL-6. To explore further the role of GM-CSF as a pro-inflammatory cytokine, we examined the effect of anti-GM-CSFRα neutralization on myeloid cell populations in antigen-driven arthritis and inflammation models and also compared its effect with that of anti-TNF and anti-IL-6...
December 1, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27891058/ido2-a-pathogenic-mediator-of-inflammatory-autoimmunity
#16
REVIEW
Lauren M F Merlo, Laura Mandik-Nayak
Indoleamine 2,3-dioxygenase 2 (IDO2), a homolog of the better-studied tryptophan-catabolizing enzyme IDO1, is an immunomodulatory molecule with potential effects on various diseases including cancer and autoimmunity. Here, we review what is known about the direct connections between IDO2 and immune function, particularly in relationship to autoimmune inflammatory disorders such as rheumatoid arthritis and lupus. Accumulating evidence indicates that IDO2 acts as a pro-inflammatory mediator of autoimmunity, with a functional phenotype distinct from IDO1...
2016: Clinical Medicine Insights. Pathology
https://www.readbyqxmd.com/read/27883001/psoriasis
#17
Jacqueline E Greb, Ari M Goldminz, James T Elder, Mark G Lebwohl, Dafna D Gladman, Jashin J Wu, Nehal N Mehta, Andrew Y Finlay, Alice B Gottlieb
Psoriasis is a chronic, immune-mediated disorder with cutaneous and systemic manifestations and substantial negative effects on patient quality of life. Psoriasis has a strong, albeit polygenic, genetic basis. Whereas approximately half of the accountable genetic effect of psoriasis maps to the major histocompatibility complex, >70 other loci have been identified, many of which implicate nuclear factor-κB, interferon signalling and the IL-23-IL-23 receptor axis. Psoriasis pathophysiology is characterized by abnormal keratinocyte proliferation and immune cell infiltration in the dermis and epidermis involving the innate and adaptive immune systems, with important roles for dendritic cells and T cells, among other cells...
November 24, 2016: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/27861821/effects-of-c2ta-genetic-polymorphisms-on-mhc-class-ii-expression-and-autoimmune-diseases
#18
Anthony C Y Yau, Fredrik Piehl, Tomas Olsson, Rikard Holmdahl
Antigen presentation by the MHC-II to CD4(+) T cells is important in adaptive immune responses. The class II transactivator (CIITA in human and C2TA in mouse) is the master regulator of MHC-II gene expression. It coordinates the transcription factors necessary for the transcription of MHC-II molecules. In humans, genetic variations in CIITA have been associated with differential expression of MHC-II and susceptibility to autoimmune diseases. Here we made use of a C2ta congenic mouse strain (expressing MHC-II haplotype H-2(q) ) to investigate the effect of the natural genetic polymorphisms in type I promoter of C2ta on MHC-II expression and function...
November 15, 2016: Immunology
https://www.readbyqxmd.com/read/27826300/treatment-with-dexamethasone-and-monophosphoryl-lipid-a-removes-disease-associated-transcriptional-signatures-in-monocyte-derived-dendritic-cells-from-rheumatoid-arthritis-patients-and-confers-tolerogenic-features
#19
Paulina A García-González, Katina Schinnerling, Alejandro Sepúlveda-Gutiérrez, Jaxaira Maggi, Lorena Hoyos, Rodrigo A Morales, Ahmed M Mehdi, Hendrik J Nel, Lilian Soto, Bárbara Pesce, María Carmen Molina, Miguel Cuchacovich, Milton L Larrondo, Óscar Neira, Diego Francisco Catalán, Catharien M Hilkens, Ranjeny Thomas, Ricardo A Verdugo, Juan C Aguillón
Tolerogenic dendritic cells (TolDCs) are promising tools for therapy of autoimmune diseases, such as rheumatoid arthritis (RA). Here, we characterize monocyte-derived TolDCs from RA patients modulated with dexamethasone and activated with monophosphoryl lipid A (MPLA), referred to as MPLA-tDCs, in terms of gene expression, phenotype, cytokine profile, migratory properties, and T cell-stimulatory capacity in order to explore their suitability for cellular therapy. MPLA-tDCs derived from RA patients displayed an anti-inflammatory profile with reduced expression of co-stimulatory molecules and high IL-10/IL-12 ratio, but were capable of migrating toward the lymphoid chemokines CXCL12 and CCL19...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27799933/ectopic-lymphoid-structures-powerhouse-of-autoimmunity
#20
REVIEW
Elisa Corsiero, Alessandra Nerviani, Michele Bombardieri, Costantino Pitzalis
Ectopic lymphoid structures (ELS) often develop at sites of inflammation in target tissues of autoimmune diseases, such as rheumatoid arthritis, Sjögren's syndrome, multiple sclerosis, myasthenia gravis, and systemic lupus erythematosus. ELS are characterized by the formation of organized T/B cells aggregates, which can acquire follicular dendritic cells network supporting an ectopic germinal center response. In this review, we shall summarize the mechanisms that regulate the formation of ELS in tertiary lymphoid organs, with particular emphasis on the role of lymphoid chemokines in both formation and maintenance of ELS, the role of emerging positive and negative regulators of ELS development and function, including T follicular helper cells and IL-27, respectively...
2016: Frontiers in Immunology
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