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Dendritic cell and arthritis

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https://www.readbyqxmd.com/read/29765156/%C3%AE-%C3%AE-tcr-regulates-production-of-interleukin-27-by-neutrophils-and-attenuates-inflammatory-arthritis
#1
Laura Bouchareychas, Eva M Grössinger, Mincheol Kang, Iannis E Adamopoulos
γδ T cells have been implicated in inflammatory diseases as an important link between the innate and adaptive immune responses, however, their role in inflammatory arthritis remain unclear. To define the contribution of γδ T cells in the pathogenesis of inflammatory arthritis, we performed gene transfer of IL-23 in B10.RIII mice to establish joint inflammation in the presence or absence of γδ T cells. We demonstrated that γδ T cell blockade has a protective effect on arthritis incidence and severity by preventing neutrophil accumulation in the blood, spleen and bone marrow as well as by reducing neutrophil infiltration into the joints...
May 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29760702/emerging-concepts-in-immune-thrombocytopenia
#2
REVIEW
Maurice Swinkels, Maaike Rijkers, Jan Voorberg, Gestur Vidarsson, Frank W G Leebeek, A J Gerard Jansen
Immune thrombocytopenia (ITP) is an autoimmune disease defined by low platelet counts which presents with an increased bleeding risk. Several genetic risk factors (e.g., polymorphisms in immunity-related genes) predispose to ITP. Autoantibodies and cytotoxic CD8+ T cells (Tc) mediate the anti-platelet response leading to thrombocytopenia. Both effector arms enhance platelet clearance through phagocytosis by splenic macrophages or dendritic cells and by induction of apoptosis. Meanwhile, platelet production is inhibited by CD8+ Tc targeting megakaryocytes in the bone marrow...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29731463/-diagnosis-and-treatment-of-rheumatoid-arthritis-toward-the-best-practice-best-practice-in-the-use-of-t-cell-co-stimulatory-inhibitor-for-patients-with-rheumatoid-arthritis
#3
Shinsuke Yasuda
CTLA4 abolishes interaction between CD28 on T cells and B7 molecules on antigen presenting cells. CTLA4-Ig, abatacept(ABT)was developed as a drug with multipotent inhibitor against activated T/B cells, monocytes, dendritic cells, macrophages and osteoclast progenitors expressing B7 molecules. In phase Ⅲ RCTs, clinical effects of ABT have been established in MTX-naive, MTX-IR and TNF inhibitor-IR patients with RA. Moreover, in head-to head comparison with representative TNF inhibitors, ABT exerted compatible clinical effect...
2018: Clinical Calcium
https://www.readbyqxmd.com/read/29729445/emerging-role-of-il-35-in-inflammatory-autoimmune-diseases
#4
REVIEW
Lin-Chong Su, Xiao-Yan Liu, An-Fang Huang, Wang-Dong Xu
Interleukin 35 (IL-35) is the recently identified member of the IL-12 family of cytokines and provides the possibility to be a target for new therapies for autoimmune, inflammatory diseases. It is composed of an α chain (p35) and a β chain (EBI3). IL-35 mediates signaling by binding to its receptors, activates subsequent signaling pathways, and therefore, regulates the differentiation, function of T, B cells, macrophages, dendritic cells. Recent findings have shown abnormal expression of IL-35 in inflammatory autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, type 1 diabetes, psoriasis, multiple sclerosis, autoimmune hepatitis, experimental autoimmune uveitis...
May 3, 2018: Autoimmunity Reviews
https://www.readbyqxmd.com/read/29720240/integrative-analysis-reveals-cd38-as-a-therapeutic-target-for-plasma-cell-rich-pre-disease-and-established-rheumatoid-arthritis-and-systemic-lupus-erythematosus
#5
Suzanne Cole, Alice Walsh, Xuefeng Yin, Mihir D Wechalekar, Malcolm D Smith, Susanna M Proudman, Douglas J Veale, Ursula Fearon, Costantino Pitzalis, Frances Humby, Michele Bombardieri, Amy Axel, Homer Adams, Christopher Chiu, Michael Sharp, John Alvarez, Ian Anderson, Loui Madakamutil, Sunil Nagpal, Yanxia Guo
BACKGROUND: Plasmablasts and plasma cells play a key role in many autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This study was undertaken to evaluate the potential of targeting CD38 as a plasma cell/plasmablast depletion mechanism by daratumumab in the treatment of patients with RA and SLE. METHODS: RNA-sequencing analysis of synovial biopsies from various stages of RA disease progression, flow cytometry analysis of peripheral blood mononuclear cells (PBMC) from patients with RA or SLE and healthy donors, immunohistochemistry assessment (IHC) of synovial biopsies from patients with early RA, and ex vivo immune cell depletion assays using daratumumab (an anti-CD38 monoclonal antibody) were used to assess CD38 as a therapeutic target...
May 2, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29717662/the-role-of-bruton-s-tyrosine-kinase-in-immune-cell-signaling-and-systemic-autoimmunity
#6
Jasper Rip, Esmee K Van Der Ploeg, Rudi W Hendriks, Odilia B J Corneth
Bruton's tyrosine kinase (BTK) is an intracellular signaling molecule first identified as the molecule affected in X-linked agammaglobulinemia (XLA) patients, who almost completely lack peripheral B cells and serum immunoglobulins. BTK is crucial for B cell development and various B cell functions, including cytokine and natural antibody production. Importantly, it is also expressed in numerous other cells, including monocytes, macrophages, granulocytes, dendritic cells, and osteoclasts. A few rare cases of autoimmune disease in XLA patients have been described...
2018: Critical Reviews in Immunology
https://www.readbyqxmd.com/read/29716677/one-year-in-review-2018-pathogenesis-of-rheumatoid-arthritis
#7
REVIEW
Emanuele Calabresi, Fiorella Petrelli, Angelo Francesco Bonifacio, Ilaria Puxeddu, Alessia Alunno
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that primarily affects joints. The several mechanisms involved in the development of the disease are not completely understood. It has been proposed that different environmental factors, such as cigarette smoking, occupational and atmospheric agents act as trigger stimuli for the development of RA in genetically predisposed individuals, leading to synovial hyperplasia and bone destruction. The initial disease stage of RA is associated with alteration of innate and adaptive immune system with consequent production of autoantibodies, targeting various molecules including modified self-epitopes...
March 2018: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/29609005/decreased-pd-1-expression-on-circulating-cd4-t-cell-and-pd-l1-expression-on-myeloid-dendritic-cells-correlate-with-clinical-manifestations-in-systemic-juvenile-idiopathic-arthritis
#8
Li Cai, Chenxing Zhang, Jing Wu, Wei Zhou, Tongxin Chen
OBJECTIVES: Programmed cell death-1 (PD-1) and its ligand (PD-L1) mediate negative signal in autoimmune diseases. While little is known about its role in juvenile idiopathic arthritis (JIA). The study aimed to reveal the circulating cell profile and the relative PD-1/PD-L1 expression of JIA subsets, elucidating their underlying immunomodulatory mechanisms. METHODS: We detected the circulating cells and the relative PD-1/PD-L1 signaling in 101 JIA patients and 50 controls by flowcytometry and analyzed their association with disease activity and clinical manifestations...
March 30, 2018: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/29568073/interrupting-oral-infection-of-porphyromonas-gingivalis-with-anti-fima-antibody-attenuates-bacterial-dissemination-to-the-arthritic-joint-and-improves-experimental-arthritis
#9
Sang Hoon Jeong, Yoojun Nam, Hyerin Jung, Juryun Kim, Yeri Alice Rim, Narae Park, Kijun Lee, Seungjin Choi, Yeonsue Jang, Yena Kim, Ji-Hoi Moon, Seung Min Jung, Sung-Hwan Park, Ji Hyeon Ju
Rheumatoid arthritis (RA) is a chronic autoimmune disease that typically results in strong inflammation and bone destruction in the joints. It is generally known that the pathogenesis of RA is linked to cardiovascular and periodontal diseases. Though rheumatoid arthritis and periodontitis share many pathologic features such as a perpetual inflammation and bone destruction, the precise mechanism underlying a link between these two diseases has not been fully elucidated. Collagen-induced arthritis (CIA) mice were orally infected with Porphyromonas gingivalis (Pg) or Pg preincubated with an anti-FimA antibody (FimA Ab) specific for fimbriae that are flexible appendages on the cell surface...
March 23, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29563728/aggressive-angioimmunoblastic-t-cell-lymphomas-aitl-with-soft-tissue-extranodal-mass-varied-histopathological-patterns-with-peripheral-blood-bone-marrow-and-splenic-involvement-and-review-of-literature
#10
Tanushri Mukherjee, Rajat Dutta, S Pramanik
Angioimmunoblastic T cell lymphoma (AITL) is a peripheral T cell non-Hodgkin lymphoma with an aggressive fatal course and it has varied clinical presentation with an uncommon presentation when they present as soft tissue masses or when there is spill in the peripheral blood or there are composite lymphomas that are rare presentations. Common presentations include lymphadenopathy, fever and systemic symptoms, hemolytic anemias, skin rashes, and rheumatoid arthritis. The classical histopathology is absence of follicles in lymph nodes with presence of high endothelial venules and the tumor cells of small to medium-sized lymphocytes with pale cytoplasm mixed with reactive T cells...
March 2018: Indian Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29554943/methotrexate-inhibits-effects-of-platelet-derived-growth-factor-and-interleukin-1%C3%AE-on-rheumatoid-arthritis-fibroblast-like-synoviocytes
#11
Beatrice Bergström, Hans Carlsten, Anna-Karin Hultgård Ekwall
BACKGROUND: A key feature of joints in rheumatoid arthritis (RA) is the formation of hyperplastic destructive pannus tissue, which is orchestrated by activated fibroblast-like synoviocytes (FLS). We have demonstrated that the RA risk gene and tumor suppressor Limb bud and heart development (LBH) regulates cell cycle progression in FLS. Methotrexate (MTX) is the first-line treatment for RA, but its mechanisms of action remain incompletely understood. Here, we studied the effects of MTX on mitogen-induced FLS proliferation and expression of cell cycle regulators in vitro...
March 20, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29519620/therapeutic-perspectives-for-interferons-and-plasmacytoid-dendritic-cells-in-rheumatoid-arthritis
#12
REVIEW
Ramzi Nehmar, Alexandre Mariotte, Aurore de Cauwer, Jean Sibilia, Seiamak Bahram, Philippe Georgel
Rheumatoid arthritis (RA) is a multifactorial immune disease exhibiting diverse clinical responses to specific therapeutic agents. Such heterogeneity reflects variable activation of signaling pathways. Consequently, RA physiopathology has been linked to many immune cells and factors, with controversial observations for interferons (IFNs). In this opinion article, we review the roles of these cytokines and the cells that produce them in light of recent data: clinical observations showing that expression of IFN-dependent genes does not reflect RA activity and RA mouse models in which the stimulation of IFN-dependent pathways provided disease protection...
April 2018: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29502227/decreased-igg4-acpa-levels-in-responders-and-increased-cd1c-classical-dendritic-cells-in-non-responders-of-patients-with-rheumatoid-arthritis-under-therapy
#13
Robby Engelmann, Sven Nekarda, Daniela Kuthning, Christian Kneitz, Brigitte Müller-Hilke
The treatment options for patients suffering from rheumatoid arthritis expanded over the last years. However, reliable biomarkers to guide therapy decisions are still warranted. Therefore, we here evaluated the value of antibodies against citrullinated peptide antigens (ACPA) IgG subclasses and peripheral blood antigen presenting cells as biomarkers to monitor and predict therapy response of patients with rheumatoid arthritis. Thirty-four ACPA-positive RA patients were enrolled and monitored for 3 months after therapy begin...
March 3, 2018: Clinical Rheumatology
https://www.readbyqxmd.com/read/29494692/il-12-23p40-overproduction-by-dendritic-cells-leads-to-an-increased-th1-and-th17-polarization-in-a-model-of-yersinia-enterocolitica-induced-reactive-arthritis-in-tnfrp55-mice
#14
Andrea Constanza Mayordomo, Juan Eduardo Silva, Carolina Virginia Gorlino, José Luis Arias, Walter Berón, María Silvia Di Genaro
Dendritic cells (DCs) play critical functions in the initiation of immune responses. Understanding their role in reactive arthritis (ReA) will help delineate the pathogenesis of this arthropathy. In early studies, we detected IL-12/23p40 deregulation in Yersinia entercolitica (Ye)-induced ReA in TNFRp55-deficient (TNFRp55-/-) mice. In this study, we assessed the contribution of DCs in this overproduction. First, greater levels of IL-12/23p40, IFN-γand IL-17A were confirmed in supernatants of lipopolysaccharide (LPS)-stimulated TNFRp55-/-splenocytes obtained on arthritis onset (day 14 after Ye infection)...
2018: PloS One
https://www.readbyqxmd.com/read/29490676/pharmacological-characterisation-of-cr6086-a-potent-prostaglandin-e-2-receptor-4-antagonist-as-a-new-potential-disease-modifying-anti-rheumatic-drug
#15
Gianfranco Caselli, Albino Bonazzi, Marco Lanza, Flora Ferrari, Daniele Maggioni, Cristian Ferioli, Roberto Giambelli, Eleonora Comi, Silvia Zerbi, Marco Perrella, Ornella Letari, Elena Di Luccio, Milena Colovic, Stefano Persiani, Tiziano Zanelli, Laura Mennuni, Tiziana Piepoli, Lucio Claudio Rovati
BACKGROUND: Prostaglandin E2 (PGE2 ) acts via its EP4 receptor as a cytokine amplifier (e.g., interleukin [IL]-6) and induces the differentiation and expansion of inflammatory T-helper (Th) lymphocytes. These mechanisms play a key role in the onset and progression of rheumatoid arthritis (RA). We present the pharmacological characterisation of CR6086, a novel EP4 receptor antagonist, and provide evidence for its potential as a disease-modifying anti-rheumatic drug (DMARD). METHODS: CR6086 affinity and pharmacodynamics were studied in EP4-expressing HEK293 cells by radioligand binding and cyclic adenosine monophosphate (cAMP) production, respectively...
March 1, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29358281/visualising-the-interaction-of-cd4-t-cells-and-dcs-in-the-evolution-of-inflammatory-arthritis
#16
Catriona T Prendergast, Agapitos Patakas, Shaima Al-Khabouri, Claire L McIntyre, Iain B McInnes, James M Brewer, Paul Garside, Robert A Benson
OBJECTIVES: Successful early intervention in rheumatoid arthritis (RA) with the aim of resetting immunological tolerance requires a clearer understanding of how specificity, cellular kinetics and spatial behaviour shape the evolution of articular T cell responses. We aimed to define initial seeding of articular CD4+ T cell responses in early experimental arthritis, evaluating their dynamic behaviour and interactions with dendritic cells (DCs) in the inflamed articular environment. METHODS: Antigen-induced arthritis was used to model articular inflammation...
April 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29324391/sirna-mediated-c-rel-knockdown-ameliorates-collagen-induced-arthritis-in-mice
#17
Tingting Fan, Fuhua Zhong, Ruiling Liu, Youhai H Chen, Ting Wang, Qingguo Ruan
Previous studies have shown that inflammatory mediators involved in the development of rheumatoid arthritis (RA) are regulated by the Rel/nuclear factor-κB (Rel/NF-κB) transcription factor family. c-Rel, a member of the Rel/NF-κB family that is preferentially expressed by immune cells, is a risk factor for several inflammatory diseases including RA. In the current study, we investigated whether targeting c-Rel can be used to treat collagen-induced arthritis, an animal model for RA. c-Rel specific siRNA (siRel) delivered by nanoparticles was used to knockdown the expression of c-Rel...
March 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29285146/isoforskolin-downregulates-proinflammatory-responses-induced-by-borrelia-burgdorferi-basic-membrane-protein-a
#18
Hua Zhao, Aihua Liu, Longqiang Shen, Cuiping Xu, Ziwei Zhu, Jiaru Yang, Xinling Han, Fukai Bao, Weimin Yang
The plant Coleus forskohlii is distributed primarily in India, Thailand, China, Egypt and Brazil and has a history of use in the treatment of multiple diseases. Isoforskolin (ISOF) is the principle active component of C. forskohlii native to China and has previously been studied for its biological effects. The aim of the present study was to evaluate the effect of ISOF on the proinflammatory responses induced by recombinant Borrelia burgdorferi basic membrane protein A (rBmpA). In in vitro experiments, the proinflammatory effects of rBmpA and the anti-inflammatory function of ISOF were evaluated in murine macrophages, human macrophages and dendritic cells by detecting the transcription and expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29250057/update-on-dendritic-cell-induced-immunological-and-clinical-tolerance
#19
REVIEW
Carolina Obregon, Rajesh Kumar, Manuel Antonio Pascual, Giuseppe Vassalli, Déla Golshayan
Dendritic cells (DCs) as highly efficient antigen-presenting cells are at the interface of innate and adaptive immunity. As such, they are key mediators of immunity and antigen-specific immune tolerance. Due to their functional specialization, research efforts have focused on the characterization of DCs subsets involved in the initiation of immunogenic responses and in the maintenance of tissue homeostasis. Tolerogenic DCs (tolDCs)-based therapies have been designed as promising strategies to prevent and control autoimmune diseases as well as allograft rejection after solid organ transplantation (SOT)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29193036/cxcl4-is-a-novel-inducer-of-human-th17-cells-and-correlates-with-il-17-and-il-22-in-psoriatic-arthritis
#20
Alsya J Affandi, Sandra C Silva-Cardoso, Samuel Garcia, Emmerik F A Leijten, Tessa S van Kempen, Wioleta Marut, Joel A G van Roon, Timothy R D J Radstake
CXCL4 regulates multiple facets of the immune response and is highly upregulated in various Th17-associated rheumatic diseases. However, whether CXCL4 plays a direct role in the induction of IL-17 production by human CD4+ T cells is currently unclear. Here, we demonstrated that CXCL4 induced human CD4+ T cells to secrete IL-17 that co-expressed IFN-γ and IL-22, and differentiated naïve CD4+ T cells to become Th17-cytokine producing cells. In a co-culture system of human CD4+ T cells with monocytes or myeloid dendritic cells, CXCL4 induced IL-17 production upon triggering by superantigen...
March 2018: European Journal of Immunology
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