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Dendritic cell and arthritis

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https://www.readbyqxmd.com/read/29324391/sirna-mediated-c-rel-knockdown-ameliorates-collagen-induced-arthritis-in-mice
#1
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...
January 8, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29285146/isoforskolin-downregulates-proinflammatory-responses-induced-by-borrelia-burgdorferi-basic-membrane-protein-a
#2
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
#3
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
#4
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 IFNγ 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...
November 29, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29124710/ultraviolet-irradiation-of-blood-the-cure-that-time-forgot
#5
Michael R Hamblin
Ultraviolet blood irradiation (UBI) was extensively used in the 1940s and 1950s to treat many diseases including septicemia, pneumonia, tuberculosis, arthritis, asthma and even poliomyelitis. The early studies were carried out by several physicians in USA and published in the American Journal of Surgery. However with the development of antibiotics, UBI use declined and it has now been called "the cure that time forgot". Later studies were mostly performed by Russian workers and in other Eastern countries and the modern view in Western countries is that UBI remains highly controversial...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29100671/-nettling-the-host-breaking-of-tolerance-in-chronic-inflammation-and-chronic-infection
#6
REVIEW
Sladjana Skopelja-Gardner, Jonathan D Jones, William F C Rigby
How and why we break tolerance to self-proteins still remains a largely unanswered question. Neutrophils have been identified as a rich source of autoantigens in a wide array of autoimmune diseases that arise as a consequence of different environmental and genetic factors, e.g. rheumatoid arthritis (RA), lupus, vasculitis, cystic fibrosis (CF) etc. Specifically, neutrophil extracellular trap (NET) formation has been identified as a link between innate and adaptive immune responses in autoimmunity. Autoantigens including neutrophil granular proteins (targeted by anti-neutrophil cytoplasmic antibodies, ANCA) as well as post-translationally modified proteins, i...
October 31, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29093987/targeting-the-epitope-spreader-pep19-by-na%C3%A3-ve-human-cd45ra-regulatory-t-cells-dictates-a-distinct-suppressive-t-cell-fate-in-a-novel-form-of-immunotherapy
#7
Hyun-Joo Kim, Gil Sun Cha, Ji-Young Joo, Juyoun Lee, Sung-Jo Kim, Jeongae Lee, So Youn Park, Jeomil Choi
Purpose: Beyond the limited scope of non-specific polyclonal regulatory T cell (Treg)-based immunotherapy, which depends largely on serendipity, the present study explored a target Treg subset appropriate for the delivery of a novel epitope spreader Pep19 antigen as part of a sophisticated form of immunotherapy with defined antigen specificity that induces immune tolerance. Methods: Human polyclonal CD4(+)CD25(+)CD127(lo-) Tregs (127-Tregs) and naïve CD4(+)CD25(+)CD45RA(+) Tregs (45RA-Tregs) were isolated and were stimulated with target peptide 19 (Pep19)-pulsed dendritic cells in a tolerogenic milieu followed by ex vivo expansion...
October 2017: Journal of Periodontal & Implant Science
https://www.readbyqxmd.com/read/29075262/clinical-tolerogenic-dendritic-cells-exploring-therapeutic-impact-on-human-autoimmune-disease
#8
REVIEW
Brett Eugene Phillips, Yesica Garciafigueroa, Massimo Trucco, Nick Giannoukakis
Tolerogenic dendritic cell (tDC)-based clinical trials for the treatment of autoimmune diseases are now a reality. Clinical trials are currently exploring the effectiveness of tDC to treat autoimmune diseases of type 1 diabetes mellitus, rheumatoid arthritis, multiple sclerosis (MS), and Crohn's disease. This review will address tDC employed in current clinical trials, focusing on cell characteristics, mechanisms of action, and clinical findings. To date, the publicly reported human trials using tDC indicate that regulatory lymphocytes (largely Foxp3+ T-regulatory cell and, in one trial, B-regulatory cells) are, for the most part, increased in frequency in the circulation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29075103/amelioration-of-collagen-induced-arthritis-using-antigen-loaded-dendritic-cells-modified-with-nf-%C3%AE%C2%BAb-decoy-oligodeoxynucleotides
#9
Hongmei Jiang, Henggui Hu, Yali Zhang, Ping Yue, Lichang Ning, Yan Zhou, Ping Shi, Rui Yuan
Dendritic cells (DCs) play an important role in the initiation of autoimmunity in rheumatoid arthritis (RA); therefore, the use of DCs needs to be explored to develop new therapeutic approaches for RA. Here, we investigated the therapeutic effect of bovine type II collagen (BIIC)-loaded DCs modified with NF-κB decoy oligodeoxynucleotides (ODNs) on collagen-induced arthritis (CIA) in rats and explored the underlying mechanisms. DCs treated with BIIC and NF-κB decoy ODNs exhibited features of immature DCs with low levels of costimulatory molecule (CD80 and CD86) expression...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29074827/-update-on-recent-progress-in-vitamin-d-research-the-effects-of-vitamin-d-in-autoinflammatory-diseases
#10
Tomoka Ao, Junichi Kikuta, Masaru Ishii
Various kinds of immune cells -including dendritic cells, macrophages, T cells and B cells- express the vitamin D receptor and 1α-hydroxylase(CYP27B1). In vitro studies have shown the anti-inflammatory effect of 1,25-dihydroxyvitamin D:the active form of vitamin D. As vitamin D deficiency spread in our society, epidemiological studies have established the association between vitamin D deficiency and incidence or progression of several inflammatory diseases, including rheumatoid arthritis(RA), systemic lupus erythematosus(SLE), and multiple sclerosis(MS)...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/29062314/harnessing-apoptotic-cell-clearance-to-treat-autoimmune-arthritis
#11
REVIEW
Philippe Saas, Francis Bonnefoy, Eric Toussirot, Sylvain Perruche
Early-stage apoptotic cells possess immunomodulatory properties. Proper apoptotic cell clearance during homeostasis has been shown to limit subsequent immune responses. Based on these observations, early-stage apoptotic cell infusion has been used to prevent unwanted inflammatory responses in different experimental models of autoimmune diseases or transplantation. Moreover, this approach has been shown to be feasible without any toxicity in patients undergoing allogeneic hematopoietic cell transplantation to prevent graft-versus-host disease...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29040339/protein-tyrosine-phosphatase-ptpn22-is-dispensable-for-dendritic-cell-antigen-processing-and-promotion-of-t-cell-activation-by-dendritic-cells
#12
Fiona Clarke, Christine K Jordan, Enrique Gutiérrez-Martinez, Jack A Bibby, Cristina Sanchez-Blanco, Georgina H Cornish, Xuezhi Dai, David J Rawlings, Rose Zamoyska, Pierre Guermonprez, Andrew P Cope, Harriet A Purvis
The PTPN22R620W single nucleotide polymorphism increases the risk of developing multiple autoimmune diseases including type 1 diabetes, rheumatoid arthritis and lupus. PTPN22 is highly expressed in antigen presenting cells (APCs) where the expression of the murine disease associated variant orthologue (Ptpn22R619W) is reported to dysregulate pattern recognition receptor signalling in dendritic cells (DCs) and promote T-cell proliferation. Because T-cell activation is dependent on DC antigen uptake, degradation and presentation, we analysed the efficiency of these functions in splenic and GM-CSF bone marrow derived DC from wild type (WT), Ptpn22-/- or Ptpn22R619W mutant mice...
2017: PloS One
https://www.readbyqxmd.com/read/29027570/are-we-right-to-consider-mesenchymal-stem-cells-to-be-a-new-perspective-for-patients-with-juvenile-idiopathic-arthritis
#13
REVIEW
Krzysztof Orczyk, Elzbieta Smolewska
Juvenile idiopathic arthritis (JIA) is the most common cause of chronic arthritis in childhood. Up to 50% of patients are resistant to standard therapy, which includes non-steroid anti-inflammatory drugs, corticosteroids, disease-modifying anti-rheumatic drugs and biologic therapies. Intra-articular injection of mesenchymal stem cells (MSCs) is proposed as a new approach to JIA treatment. MSCs can modulate inflammation via mechanisms of both adaptive and innate immune response. They are able to inhibit T and B cell proliferation, promote regulatory T cells, suppress the maturation of dendritic cells, stimulate macrophage differentiation into M2 phenotype and reduce effectiveness of natural killer cells...
October 13, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28978351/the-caspase-8-ripk3-signaling-axis-in-antigen-presenting-cells-controls-the-inflammatory-arthritic-response
#14
Salina Dominguez, Anna B Montgomery, G Kenneth Haines, Christina L Bloomfield, Carla M Cuda
BACKGROUND: Caspase-8 is a well-established initiator of apoptosis and suppressor of necroptosis, but maintains functions beyond cell death that involve suppression of receptor-interacting serine-threonine kinases (RIPKs). A genome-wide association study meta-analysis revealed an SNP associated with risk of rheumatoid arthritis (RA) development within the locus containing the gene encoding for caspase-8. Innate immune cells, like macrophages and dendritic cells, are gaining momentum as facilitators of autoimmune disease pathogenesis, and, in particular, RA...
October 4, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28957552/enrichment-of-malondialdehyde-acetaldehyde-antibody-in-the-rheumatoid-arthritis-joint
#15
Ted R Mikuls, Michael J Duryee, Rafid Rahman, Daniel R Anderson, Harlan R Sayles, Andrew Hollins, Kaleb Michaud, Frederick Wolfe, Geoffrey E Thiele, Jeremy Sokolove, William H Robinson, Nithya Lingampalli, Anthony P Nicholas, Geoffrey A Talmon, Kaihong Su, Matthew C Zimmerman, Lynell W Klassen, Geoffrey M Thiele
Objective: To characterize the expression of malondialdehdye-acetaldehyde (MAA) adducts and anti-MAA antibody in articular tissues and serum of patients with RA. Methods: Paired sera and SF were examined from 29 RA and 13 OA patients. Anti-MAA antibody, RF, ACPA and total immunoglobulin were quantified. SF-serum measures were compared within and between disease groups. The presence and co-localization of MAA, citrulline and select leukocyte antigens in RA and OA synovial tissues were examined using immunohistochemistry...
October 1, 2017: Rheumatology
https://www.readbyqxmd.com/read/28948613/protein-tyrosine-phosphatase-ptpn22-regulates-il-1%C3%AE-dependent-th17-responses-by-modulating-dectin-1-signaling-in-mice
#16
Harriet A Purvis, Fiona Clarke, Christine K Jordan, Cristina Sanchez Blanco, Georgina H Cornish, Xuezhi Dai, David J Rawlings, Rose Zamoyska, Andrew P Cope
A single nucleotide polymorphism within the PTPN22 gene is a strong genetic risk factor predisposing to the development of multiple autoimmune diseases. PTPN22 regulates Syk and Src family kinases downstream of immuno-receptors. Fungal β-glucan receptor dectin-1 signals via Syk, and dectin-1 stimulation induces arthritis in mouse models. We investigated whether PTPN22 regulates dectin-1 dependent immune responses. Bone marrow derived dendritic cells (BMDCs) generated from C57BL/6 wild type (WT) and Ptpn22(-/-) mutant mice, were pulsed with OVA323-339 and the dectin-1 agonist curdlan and co-cultured in vitro with OT-II T-cells or adoptively transferred into OT-II mice, and T-cell responses were determined by immunoassay...
September 25, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28947947/discovery-of-cdz173-leniolisib-representing-a-structurally-novel-class-of-pi3k-delta-selective-inhibitors
#17
Klemens Hoegenauer, Nicolas Soldermann, Frédéric Zécri, Ross S Strang, Nadege Graveleau, Romain M Wolf, Nigel G Cooke, Alexander B Smith, Gregory J Hollingworth, Joachim Blanz, Sascha Gutmann, Gabriele Rummel, Amanda Littlewood-Evans, Christoph Burkhart
The predominant expression of phosphoinositide 3-kinase δ (PI3Kδ) in leukocytes and its critical role in B and T cell functions led to the hypothesis that selective inhibitors of this isoform would have potential as therapeutics for the treatment of allergic and inflammatory disease. Targeting specifically PI3Kδ should avoid potential side effects associated with the ubiquitously expressed PI3Kα and β isoforms. We disclose how morphing the heterocyclic core of previously discovered 4,6-diaryl quinazolines to a significantly less lipophilic 5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine, followed by replacement of one of the phenyl groups with a pyrrolidine-3-amine, led to a compound series with an optimal on-target profile and good ADME properties...
September 14, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28946117/sappanone-a-inhibits-rankl-induced-osteoclastogenesis-in-bmms-and-prevents-inflammation-mediated-bone-loss
#18
Young-Yeon Choo, Phuong Thao Tran, Byung-Sun Min, Okwha Kim, Hai Dang Nguyen, Seung-Hae Kwon, Jeong-Hyung Lee
Receptor activator of nuclear factor-kB ligand (RANKL) is a key factor in the differentiation and activation of osteoclasts. Suppressing osteoclastogenesis is considered an effective therapeutic approach for bone-destructive diseases, such as osteoporosis and rheumatoid arthritis. Sappanone A (SPNA), a homoisoflavanone compound isolated from the heartwood of Caesalpinia sappan, has been reported to exert anti-inflammatory effects; however, the effects of SPNA on osteoclastogenesis have not been investigated...
September 22, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28935693/a-multidimensional-blood-stimulation-assay-reveals-immune-alterations-underlying-systemic-juvenile-idiopathic-arthritis
#19
Alma-Martina Cepika, Romain Banchereau, Elodie Segura, Marina Ohouo, Brandi Cantarel, Kristina Goller, Victoria Cantrell, Emily Ruchaud, Elizabeth Gatewood, Phuong Nguyen, Jinghua Gu, Esperanza Anguiano, Sandra Zurawski, Jeanine M Baisch, Marilynn Punaro, Nicole Baldwin, Gerlinde Obermoser, Karolina Palucka, Jacques Banchereau, Sebastian Amigorena, Virginia Pascual
The etiology of sporadic human chronic inflammatory diseases remains mostly unknown. To fill this gap, we developed a strategy that simultaneously integrates blood leukocyte responses to innate stimuli at the transcriptional, cellular, and secreted protein levels. When applied to systemic juvenile idiopathic arthritis (sJIA), an autoinflammatory disease of unknown etiology, this approach identified gene sets associated with specific cytokine environments and activated leukocyte subsets. During disease remission and off treatment, sJIA patients displayed dysregulated responses to TLR4, TLR8, and TLR7 stimulation...
November 6, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28928016/cxcl14-acts-as-a-specific-carrier-of-cpg-dna-into-dendritic-cells-and-activates-toll-like-receptor-9-mediated-adaptive-immunity
#20
Kosuke Tanegashima, Rena Takahashi, Hideko Nuriya, Rina Iwase, Naoto Naruse, Kohei Tsuji, Akira Shigenaga, Akira Otaka, Takahiko Hara
CXCL14 is a primordial chemokine that plays multiple roles in tumor suppression, autoimmune arthritis, and obesity-associated insulin resistance. However, the underlying molecular mechanisms are unclear. Here, we show that CXCL14 transports various types of CpG oligodeoxynucleotide (ODN) into the endosomes and lysosomes of bone marrow-derived dendritic cells (DCs), thereby activating Toll-like receptor 9 (TLR9). A combination of CpG ODN (ODN2395) plus CXCL14 induced robust production of IL-12 p40 by wild-type, but not Tlr9-knockout, DCs...
October 2017: EBioMedicine
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