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Dendritic cell and arthritis

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https://www.readbyqxmd.com/read/28708978/methotrexate-combined-with-cyclophosphamide-attenuates-murine-collagen-induced-arthritis-by-modulating-the-expression-level-of-breg-and-dcs
#1
Jinnan Fan, Jing Luo, Caiping Yan, Runxi Hao, Xiangcong Zhao, Ruihuan Jia, Jiaojiao He, Dan Xu, Miao Miao, Xiaofeng Li
To explore the mechanism of methotrexate (MTX) and its combination with cyclophosphamide (CTX) in collagen-induced arthritis (CIA), we investigated the levels of several immune cells and cytokines in mice with different treatments. CIA was induced in DBA/1 mice at the age of 7 weeks by primary immunization with 100μl emulsion containing 2mg/ml bovine type II collagen which was mixed with complete Freund's adjuvant (CFA). The booster immunization was performed with 50-100μl emulsion containing 2mg/ml bovine type II collagen (CII) mixed with incomplete Freund's adjuvant (IFA)...
July 11, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28702462/adoptive-cell-therapy-of-induced-regulatory-t-cells-expanded-by-tolerogenic-dendritic-cells-on-murine-autoimmune-arthritis
#2
Jie Yang, Lidong Liu, Yiming Yang, Ning Kong, Xueyu Jiang, Juan Sun, Rufeng Xie
OBJECTIVE: Tolerogenic dendritic cells (tDCs) can expand TGF-β-induced regulatory T cells (iTregs); however, the therapeutic utility of these expanded iTregs in autoimmune diseases remains unknown. We sought to determine the properties of iTregs expanded by mature tolerogenic dendritic cells (iTregmtDC) in vitro and explore their potential to ameliorate collagen-induced arthritis (CIA) in a mouse model. METHODS: After induction by TGF-β and expansion by mature tDCs (mtDCs), the phenotype and proliferation of iTregmtDC were assessed by flow cytometry...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28701761/antigen-specific-immunotherapies-in-rheumatic-diseases
#3
REVIEW
Judit Pozsgay, Zoltán Szekanecz, Gabriella Sármay
The main goal of antigen-specific immunotherapy (ASI) in autoimmune and rheumatic diseases is to reprogramme or remove autoreactive cells and/or induce immune tolerance to self-antigens. Current therapies in these diseases either treat symptoms or slow down disease progression but are not yet curative or preventative - disease-specific treatments are urgently needed. In contrast to the nonspecific treatments in current use that induce generalized immune suppression, which is associated with several adverse effects including increased risk of infections, ASIs target a restricted subset of B cells or T cells, and thus do not compromise systemic immunity and host defence...
July 13, 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28639625/microrna-34a-dependent-regulation-of-axl-controls-the-activation-of-dendritic-cells-in-inflammatory-arthritis
#4
Mariola Kurowska-Stolarska, Stefano Alivernini, Emma Garcia Melchor, Aziza Elmesmari, Barbara Tolusso, Clare Tange, Luca Petricca, Derek S Gilchrist, Gabriele Di Sante, Chantal Keijzer, Lynn Stewart, Clara Di Mario, Vicky Morrison, James M Brewer, Duncan Porter, Simon Milling, Ronald D Baxter, David McCarey, Elisa Gremese, Greg Lemke, Gianfranco Ferraccioli, Charles McSharry, Iain B McInnes
Current treatments for rheumatoid arthritis (RA) do not reverse underlying aberrant immune function. A genetic predisposition to RA, such as HLA-DR4 positivity, indicates that dendritic cells (DC) are of crucial importance to pathogenesis by activating auto-reactive lymphocytes. Here we show that microRNA-34a provides homoeostatic control of CD1c(+) DC activation via regulation of tyrosine kinase receptor AXL, an important inhibitory DC auto-regulator. This pathway is aberrant in CD1c(+) DCs from patients with RA, with upregulation of miR-34a and lower levels of AXL compared to DC from healthy donors...
June 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28631608/one-year-in-review-2017-pathogenesis-of-rheumatoid-arthritis
#5
REVIEW
Francesca Angelotti, Alice Parma, Giacomo Cafaro, Riccardo Capecchi, Alessia Alunno, Ilaria Puxeddu
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease influenced by both genetic and environmental factors. It has been postulated that a high-risk genetic background, in combination with epigenetic marks and environmental exposures, leads to a cascade of events inducing synovitis and consequent destructive arthritis. The clinical picture of joint involvement in RA is the result of chronic inflammation of the synovium, characterised by interactions of resident cells such as fibroblast-like synoviocytes (FLS) with cells of the innate (e...
May 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28626064/monitoring-c3ar-expression-using-a-floxed-tdtomato-c3ar-reporter-knock-in-mouse
#6
Katharina M Quell, Christian M Karsten, Anna Kordowski, Larissa Nogueira Almeida, Daria Briukhovetska, Anna V Wiese, Jing Sun, Fanny Ender, Konstantina Antoniou, Torsten Schröder, Inken Schmudde, Johann L Berger, Peter König, Tillman Vollbrandt, Yves Laumonnier, Jörg Köhl
C3a exerts multiple biologic functions through activation of its cognate C3a receptor. C3(-/-) and C3aR(-/-) mice have been instrumental in defining important roles of the C3a/C3aR axis in the regulation of acute and chronic inflammatory diseases, including ischemia/reperfusion injury, allergic asthma, autoimmune nephritis, and rheumatoid arthritis. Surprisingly little is known about C3aR expression and function in immune and stromal cells. To close this gap, we generated a floxed tandem-dye Tomato (tdTomato)-C3aR reporter knock-in mouse, which we used to monitor C3aR expression in cells residing in the lung, airways, lamina propria (LP) of the small intestine, brain, visceral adipose tissue, bone marrow (BM), spleen, and the circulation...
June 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28606971/response-to-does-il-38-act-on-macrophages-and-or-dendritic-cells-in-arthritis-by-jiang-et-al
#7
Marie-Astrid Boutet, Frédéric Blanchard, Benoît Le Goff
No abstract text is available yet for this article.
June 12, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28598681/soluble-cd206-plasma-levels-in-rheumatoid-arthritis-reflect-decrease-in-disease-activity
#8
Line Dam Heftdal, Kristian Stengaard-Pedersen, Lykke Midtbøll Ørnbjerg, Merete Lund Hetland, Kim Hørslev-Petersen, Peter Junker, Mikkel Østergaard, Malene Hvid, Bent Deleuran, Holger Jon Møller, Stinne Ravn Greisen
Rheumatoid arthritis (RA) is characterized by chronic joint inflammation and infiltration by activated macrophages. TNFα is a central mediator in this process. The mannose receptor, CD206, is a scavenger receptor expressed by M2A-macrophages and dendritic cells. It is involved in collagen internalization and degradation. The soluble form has been suggested as a biomarker of M2A-macrophage activation. The aim of this study was to investigate sCD206 plasma levels in early RA patients initiating anti-TNFα treatment...
June 9, 2017: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/28581446/tregs-restrain-dendritic-cell-autophagy-to-ameliorate-autoimmunity
#9
Themis Alissafi, Aggelos Banos, Louis Boon, Tim Sparwasser, Alessandra Ghigo, Kajsa Wing, Dimitrios Vassilopoulos, Dimitrios Boumpas, Triantafyllos Chavakis, Ken Cadwell, Panayotis Verginis
Design of efficacious Treg-based therapies and establishment of clinical tolerance in autoimmune diseases have proven to be challenging. The clinical implementation of Treg immunotherapy has been hampered by various impediments related to the stability and isolation procedures of Tregs as well as the specific in vivo targets of Treg modalities. Herein, we have demonstrated that Foxp3+ Tregs potently suppress autoimmune responses in vivo through inhibition of the autophagic machinery in DCs in a cytotoxic T-lymphocyte-associated protein 4-dependent (CTLA4-dependent) manner...
June 30, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28578466/dopaminergic-regulation-of-innate-immunity-a-review
#10
REVIEW
Monica Pinoli, Franca Marino, Marco Cosentino
Dopamine (DA) is a neurotransmitter in the central nervous system as well as in peripheral tissues. Emerging evidence however points to DA also as a key transmitter between the nervous system and the immune system as well as a mediator produced and released by immune cells themselves. Dopaminergic pathways have received so far extensive attention in the adaptive branch of the immune system, where they play a role in health and disease such as multiple sclerosis, rheumatoid arthritis, cancer, and Parkinson's disease...
June 3, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28529069/cholinergic-modulation-of-the-immune-system-presents-new-approaches-for-treating-inflammation
#11
REVIEW
Donald B Hoover
The nervous system and immune system have broad and overlapping distributions in the body, and interactions of these ubiquitous systems are central to the field of neuroimmunology. Over the past two decades, there has been explosive growth in our understanding of neuroanatomical, cellular, and molecular mechanisms that mediate central modulation of immune functions through the autonomic nervous system. A major catalyst for growth in this field was the discovery that vagal nerve stimulation (VNS) caused a prominent attenuation of the systemic inflammatory response evoked by endotoxin in experimental animals...
May 18, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28528521/myeloid-populations-in-systemic-autoimmune-diseases
#12
REVIEW
María Morell, Nieves Varela, Concepción Marañón
Systemic autoimmune diseases (SADs) encompass a wide spectrum of clinical signs as a reflection of their complex physiopathology. A variety of mechanisms related with the innate immune system are in the origin of the loss of self-tolerance in these diseases, and for most of them, the myeloid leukocytes are key actors. Monocytes, macrophages, dendritic cells, and neutrophils are first-line immune effectors located in the interface between innate and adaptive immunity. They are crucial in the organization of the local and systemic responses to damage-associated molecular patterns (DAMPs) and determine the intensity, orientation, and duration of the local immune response through the expression of chemokines, costimulatory or protolerogenic factors...
May 20, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28511090/inactivation-of-the-ksrp-gene-modifies-collagen-antibody-induced-arthritis
#13
Rudolf Käfer, Katharina Schrick, Lisa Schmidtke, Evelyn Montermann, Dominika Hobernik, Matthias Bros, Ching-Yi Chen, Hartmut Kleinert, Andrea Pautz
The KH type splicing regulatory protein (KSRP) is a nucleic acid binding protein, which negatively regulates the stability and/or translatability of many mRNA species encoding immune-relevant proteins. As KSRP is expressed in immune cells including T and B cells, neutrophils, macrophages and dendritic cells, we wanted to analyze its importance for the development of autoimmune diseases. We chose collagen antibody-induced arthritis (CAIA) as an appropriate autoimmune disease mouse model in which neutrophils and macrophages constitute the main effector cell populations...
July 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28499587/the-phosphodiesterase-4-inhibitor-apremilast-inhibits-th1-but-promotes-th17-responses-induced-by-6-sulfo-lacnac-slan-dendritic-cells
#14
Stephanie Oehrl, Hridayesh Prakash, Annette Ebling, Nina Trenkler, Priscila Wölbing, Anja Kunze, Thomas Döbel, Marc Schmitz, Alexander Enk, Knut Schäkel
BACKGROUND: The phosphodiesterase 4 (PDE4) inhibitor apremilast increases cellular cAMP levels and has proven effective in the treatment of psoriasis and psoriasis arthritis. We recently described 6-sulfo LacNAc dendritic cells (slanDCs) as immature DCs in blood and as a subset of inflammatory dermal DCs in psoriasis with a pronounced capacity to produce proinflammatory cytokines and to program Th17/Th1 T cell responses. OBJECTIVE: The aim of this study was to investigate possible immune regulatory effects of the PDE4 inhibitor apremilast on slanDCs...
April 20, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28490801/dendritic-cells-provide-a-therapeutic-target-for-synthetic-small-molecule-analogues-of-the-parasitic-worm-product-es-62
#15
Felicity E Lumb, James Doonan, Kara S Bell, Miguel A Pineda, Marlene Corbet, Colin J Suckling, Margaret M Harnett, William Harnett
ES-62, a glycoprotein secreted by the parasitic filarial nematode Acanthocheilonema viteae, subverts host immune responses towards anti-inflammatory phenotypes by virtue of covalently attached phosphorylcholine (PC). The PC dictates that ES-62 exhibits protection in murine models of inflammatory disease and hence a library of drug-like PC-based small molecule analogues (SMAs) was synthesised. Four sulfone-containing SMAs termed 11a, 11e, 11i and 12b were found to reduce mouse bone marrow-derived dendritic cell (DC) pathogen-associated molecular pattern (PAMP)-induced pro-inflammatory cytokine production, inhibit NF-κB p65 activation, and suppress LPS-induced up-regulation of CD40 and CD86...
May 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28465419/papers-of-note-in-science-immunology2-10
#16
John F Foley
This month's articles show that cholesterol-based ligands position splenic dendritic cells near T cells; how synovial fibroblasts and neutrophils promote inflammation in arthritis; that type I interferon activates liver T cells in obese mice; and how the alternative complement pathway plays a role in antibacterial immunity.
May 2, 2017: Science Signaling
https://www.readbyqxmd.com/read/28455435/cd40l-dependent-pathway-is-active-at-various-stages-of-rheumatoid-arthritis-disease-progression
#17
Yanxia Guo, Alice M Walsh, Ursula Fearon, Malcolm D Smith, Mihir D Wechalekar, Xuefeng Yin, Suzanne Cole, Carl Orr, Trudy McGarry, Mary Canavan, Stephan Kelly, Tai-An Lin, Xuejun Liu, Susanna M Proudman, Douglas J Veale, Costantino Pitzalis, Sunil Nagpal
The inflammatory CD40-CD40L pathway is implicated in various autoimmune diseases, but the activity status of this pathway in various stages of rheumatoid arthritis (RA) progression is unknown. In this study, we used gene signatures of CD40L stimulation derived from human immature dendritic cells and naive B cells to assess the expression of CD40-downstream genes in synovial tissues from anti-citrullinated protein Ab-positive arthralgia, undifferentiated arthritis (UA), early RA, and established RA cohorts in comparison with healthy donors...
April 28, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28451787/future-therapeutic-targets-in-rheumatoid-arthritis
#18
REVIEW
Tommy Tsang Cheung, Iain B McInnes
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation. Without adequate treatment, patients with RA will develop joint deformity and progressive functional impairment. With the implementation of treat-to-target strategies and availability of biologic therapies, the outcomes for patients with RA have significantly improved. However, the unmet need in the treatment of RA remains high as some patients do not respond sufficiently to the currently available agents, remission is not always achieved and refractory disease is not uncommon...
June 2017: Seminars in Immunopathology
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
#19
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
#20
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
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