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Dendritic cell and arthritis

Zhi-Dan Fan, Ya-Yuan Zhang, Yi-Hong Guo, Na Huang, Hui-Hui Ma, Hui Huang, Hai-Guo Yu
Interleukin (IL)-17 producing T helper (Th17) cells are major effector cells in the pathogenesis of rheumatoid arthritis (RA). The P2X7 receptor (P2X7R) has emerged as a potential site in the regulation of inflammation in RA but little is known of its functional role on the differentiation of Th17 cells. This study investigates the in vitro and in vivo effects of P2X7R on Th17 cell differentiation during type II collagen (CII) induced experimental arthritis model. In CII-treated dendritic cells (DCs) and DC/CD4(+) T coculture system, pretreatment with pharmacological antagonists of P2X7R (Suramin and A-438079) caused strong inhibition of production of Th17-promoting cytokines (IL-1β, TGF-β1, IL-23p19 and IL-6)...
October 24, 2016: Scientific Reports
Meriam Nefla, Dirk Holzinger, Francis Berenbaum, Claire Jacques
Alarmins (also known as danger signals) are endogenous molecules that are released to the extracellular milieu after infection or tissue damage. Extracellular alarmins interact with specific receptors expressed by cells that are engaged in host defence to stimulate signalling pathways that result in initiation of innate and adaptive immune responses, triggering inflammation or tissue repair. Alarmins are considered to be markers of destructive processes that occur in degenerative joint diseases (primarily osteoarthritis (OA)) and chronic inflammatory joint diseases (such as rheumatoid arthritis, psoriatic arthritis and spondylarthropathy)...
October 13, 2016: Nature Reviews. Rheumatology
Susanne Mommert, Lisanne Ratz, Kira Herwig, Maren Rost, Ralf Gutzmer, Thomas Werfel
Environmental triggers and genetic factors are supposed to lead to complex gene expression changes in psoriasis and interact in the manifestation of the disease. The histamine H4 receptor (HRH4) is functionally expressed on Th17 cells and plasmacytoid dendritic cells (pDCs) which play a prominent role in the pathogenesis of psoriasis. On pDCs a higher basal expression level of the HRH4 in psoriasis patients compared to healthy controls has been detected. The functional relationship between predisposing genetic variations in the HRH4 gene and psoriasis is yet not known...
October 7, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Xuefeng Wang, Li Li, Jun Wang, Liyang Dong, Yang Shu, Yong Liang, Liang Shi, Chengcheng Xu, Yuepeng Zhou, Yi Wang, Deyu Chen, Chaoming Mao
Helminth-derived products have recently been shown to prevent the development of inflammatory diseases in mouse models. However, most identified immunomodulators from helminthes are mixtures or macromolecules with potentially immunogenic side effects. We previously identified an immunomodulatory peptide called SJMHE1 from the HSP60 protein of Schistosoma japonicum. In this study, we assessed the ability of SJMHE1 to affect murine splenocytes and human peripheral blood mononuclear cells (PBMCs) stimulated by toll-like receptor (TLR) ligands in vitro and its treatment effect on mice with collagen-induced arthritis (CIA)...
September 28, 2016: Journal of Cellular and Molecular Medicine
Amy E Anderson, David J Swan, Oi Yean Wong, Matthew Buck, Oliver Eltherington, Rachel A Harry, Angela M Patterson, Arthur G Pratt, Gary Reynolds, John-Paul Doran, John A Kirby, John D Isaacs, Catharien M U Hilkens
Tolerogenic dendritic cells (tolDC) are a new immunotherapeutic tool for the treatment of rheumatoid arthritis (RA) and other autoimmune disorders. We have established a method to generate stable tolDC by pharmacological modulation of human monocyte-derived DC. These tolDC exert potent pro-tolerogenic actions on CD4(+) T-cells. Lack of IL-12p70 production is a key immunoregulatory attribute of tolDC but does not fully explain their action. Here we show that tolDC express TGF-β1 at both mRNA and protein level, and that expression of this immunoregulatory cytokine is significantly higher in tolDC than in mature monocyte-derived DC...
September 26, 2016: Clinical and Experimental Immunology
Endy Adnan, Takuya Matsumoto, Jun Ishizaki, Sachiko Onishi, Koichiro Suemori, Masaki Yasukawa, Hitoshi Hasegawa
Tolerogenic dendritic cells (tDCs) are a promising therapeutic tool for specific induction of immunological tolerance. Human tDCs can be generated ex vivo using various compounds. However, the compound(s) most suitable for clinical application remain undefined. We compared the tolerogenic properties of tDCs treated with protein kinase C inhibitor (PKCI), dexamethasone, vitamin D3 (Vit D3), rapamycin (Rapa), interleukin (IL)-10, transforming growth factor (TGF)-β, and a combination of peroxisome proliferator-activated receptor γ agonist and retinoic acid...
September 19, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Jaya Prakash Chalise, Maria Teresa Pallotta, Sudeep Chenna Narendra, Björn Carlsson, Alberta Iacono, Joanitah Namale, Louis Boon, Ursula Grohmann, Mattias Magnusson
IFN-α prevents Ag-induced arthritis (AIA), and in this study we investigated the role of IDO1 and TGF-β signaling for this anti-inflammatory property of IFN-α. Arthritis was induced by methylated BSA (mBSA) in mBSA-sensitized wild-type (WT), Ido1(-/-), or Ifnar(-/-) mice, treated or not with IFN-α or the IDO1 product kynurenine (Kyn). Enzymatic IDO1 activity, TGF-β, and plasmacytoid dendritic cells (pDC) were neutralized by 1-methyltryptophan and Abs against TGF-β and pDC, respectively. IDO1 expression was determined by RT-PCR, Western blot, and FACS, and enzymatic activity by HPLC...
September 19, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Sy-Jye Leu, Yi-Yuan Yang, Hsing-Cheng Liu, Chieh-Yu Cheng, Yu-Chen Wu, Ming-Chyi Huang, Yuen-Lun Lee, Chi-Ching Chen, Winston W Shen, Ko-Jiunn Liu
Valproic acid (VPA), with inhibition activity mainly towards histone deacetylase (HDAC) and Glycogen Synthase Kinase (GSK)-3, and lithium, with inhibition activity mainly toward GSK-3, are both prescribed in clinical as mood-stabilizers and anticonvulsants for the control of bipolar disorder. This study aims to compare the immuno-modulation activities of VPA and lithium, especially on the differentiation and functions of dendritic cells (DC). Our data show that treatment with VPA or lithium effectively alleviated the severity of collagen-induced arthritis triggered by LPS in mice...
September 17, 2016: Journal of Cellular Physiology
M Ikić Matijašević, D Flegar, N Kovačić, V Katavić, T Kelava, A Šućur, S Ivčević, H Cvija, E Lazić Mosler, I Kalajzić, A Marušić, D Grčević
Our study aimed to determine the functional activity of different osteoclast progenitor (OCP) subpopulations and signals important for their migration to bone lesions, causing local and systemic bone resorption during the course of collagen-induced arthritis in C57BL/6 mice. Arthritis was induced with chicken type II collagen (CII), and assessed by clinical scoring and detection of anti-CII antibodies. We observed decreased trabecular bone volume of axial and appendicular skeleton by histomorphometry and micro-computed tomography as well as decreased bone formation and increased bone resorption rate in arthritic mice in vivo...
September 10, 2016: Clinical and Experimental Immunology
Garyfalia Papadaki, Konstantinos Kambas, Christiana Choulaki, Katerina Vlachou, Elias Drakos, George Bertsias, Konstantinos Ritis, Dimitrios T Boumpas, Paul R Thompson, Panayotis Verginis, Prodromos Sidiropoulos
Aberrant formation of neutrophil extracellular traps (NETs) is a key feature in rheumatoid arthritis (RA) and plays a pivotal role in disease pathogenesis. However, the mechanism through which NETs shape the autoimmune response in RA remains elusive. In this study, we demonstrate that inhibition of peptidylarginine deiminases activity in collagen-induced arthritis (CIA) mouse model significantly reduces NET formation, attenuates clinical disease activity, and prevents joint destruction. Importantly, peptidylarginine deiminase 4 blocking markedly reduces the frequency of collagen-specific IFN-γ-producing T helper 1 (Th1) cells in the draining lymph nodes of immunized mice...
September 2, 2016: European Journal of Immunology
Cheryl Stroud, Igor Dmitriev, Elena Kashentseva, Jeffrey N Bryan, David T Curiel, Hans Rindt, Carol Reinero, Carolyn J Henry, Philip J Bergman, Nicola J Mason, Josephine S Gnanandarajah, Julie B Engiles, Falon Gray, Danielle Laughlin, Anita Gaurnier-Hausser, Anu Wallecha, Margie Huebner, Yvonne Paterson, Daniel O'Connor, Laura S Treml, James P Stannard, James L Cook, Marc Jacobs, Gerald J Wyckoff, Lee Likins, Ubadah Sabbagh, Andrew Skaff, Amado S Guloy, Harlen D Hays, Amy K LeBlanc, Joan R Coates, Martin L Katz, Leslie A Lyons, Gayle C Johnson, Gary S Johnson, Dennis P O'Brien, Dongsheng Duan, James P Calvet, Barbara Gandolfi, David A Baron, Mark L Weiss, Debra A Webster, Francis N Karanu, Edward J Robb, Robert J Harman
A1 One health advances and successes in comparative medicine and translational researchCheryl StroudA2 Dendritic cell-targeted gorilla adenoviral vector for cancer vaccination for canine melanomaIgor Dmitriev, Elena Kashentseva, Jeffrey N. Bryan, David T. CurielA3 Viroimmunotherapy for malignant melanoma in the companion dog modelJeffrey N. Bryan, David Curiel, Igor Dmitriev, Elena Kashentseva, Hans Rindt, Carol Reinero, Carolyn J. HenryA4 Of mice and men (and dogs!): development of a commercially licensed xenogeneic DNA vaccine for companion animals with malignant melanomaPhilip J...
August 2016: Clinical and Translational Medicine
Xiaofei Liu, Benhua Zeng, Juan Zhang, Wenxia Li, Fangxiang Mou, Heng Wang, Qinghua Zou, Bing Zhong, Like Wu, Hong Wei, Yongfei Fang
Genetics alone cannot explain most cases of rheumatoid arthritis (RA). Thus, investigating environmental factors such as the gut microbiota may provide new insights into the initiation and progression of RA. In this study, we performed 16S rRNA sequencing to characterise the gut microbiota of DBA1 mice that did or did not develop arthritis after induction with collagen. We found that divergence in the distribution of microbiota after induction was pronounced and significant. Mice susceptible to collagen-induced arthritis (CIA) showed enriched operational taxonomic units (OTUs) affiliated with the genus Lactobacillus as the dominant genus prior to arthritis onset...
2016: Scientific Reports
Takashi K Kishimoto, Joseph D Ferrari, Robert A LaMothe, Pallavi N Kolte, Aaron P Griset, Conlin O'Neil, Victor Chan, Erica Browning, Aditi Chalishazar, William Kuhlman, Fen-Ni Fu, Nelly Viseux, David H Altreuter, Lloyd Johnston, Roberto A Maldonado
The development of antidrug antibodies (ADAs) is a common cause for the failure of biotherapeutic treatments and adverse hypersensitivity reactions. Here we demonstrate that poly(lactic-co-glycolic acid) (PLGA) nanoparticles carrying rapamycin, but not free rapamycin, are capable of inducing durable immunological tolerance to co-administered proteins that is characterized by the induction of tolerogenic dendritic cells, an increase in regulatory T cells, a reduction in B cell activation and germinal centre formation, and the inhibition of antigen-specific hypersensitivity reactions...
October 2016: Nature Nanotechnology
Sergey V Sennikov, Svetlana A Falaleeva, Nadezhda S Shkaruba, Oksana A Chumasova, Irina A Obleukhova, Aleksey E Sizikov, Vasily V Kurilin
BACKGROUND: Since dendritic cells (DC) are involved in the development of autoimmune inflammation, researchers consider DC both as target cells for specific therapy of rheumatoid arthritis (RA) and as candidate cells for the development of cell-based methods to treat autoimmune diseases. The development of treatment strategies requires comprehensive research into the quantitative and qualitative characteristics of DC subtypes both ex vivo from RA patients and in vitro, to determine the possibility of inducing functionally mature DC in RA...
October 2016: Human Immunology
Farzaneh Rahmani, Nima Rezaei
INTRODUCTION: Recent findings about the expression of various Toll-like receptors (TLR) in keratinocytes (KCs) have offered new insights into the pathogenesis of psoriasis. When plasmacytoid dendritic cells (pDCs) are scarce in established psoriatic lesions, KCs take the responsibility to secrete IFN type 1 through TLR9 activation. Wherein RNA containing immune complexes (ICs) binds to TLR7 in pDCs, KCs become hyporesponsive in response to them. Damaged KCs, DCs, neutrophils and T-cells seem to be involved in multiple positive feedback loops in Imiquimod-induced model of psoriasis...
June 30, 2016: Expert Review of Clinical Immunology
Eric V Marietta, Joseph A Murray, David H Luckey, Patricio R Jeraldo, Abhinav Lamba, Robin Patel, Harvinder S Luthra, Ashutosh Mangalam, Veena Taneja
OBJECTIVE: The gut microbiome regulates host immune homeostasis. Rheumatoid arthritis (RA) is associated with intestinal dysbiosis. In this study we used a human gut-derived commensal to modulate immune response and treat arthritis in a humanized mouse model. METHODS: We have isolated a commensal bacterium, Prevotella histicola, native to the human gut that has systemic immune effects when administered enterally. Arthritis-susceptible HLA-DQ8 mice were immunized with type II collagen and treated with P...
June 23, 2016: Arthritis & Rheumatology
Yuichi Maeda, Takashi Kurakawa, Eiji Umemoto, Daisuke Motooka, Yoshinaga Ito, Kazuyoshi Gotoh, Keiji Hirota, Masato Matsushita, Yoki Furuta, Masashi Narazaki, Noriko Sakaguchi, Hisako Kayama, Shota Nakamura, Tetsuya Iida, Yukihiko Saeki, Atsushi Kumanogoh, Shimon Sakaguchi, Kiyoshi Takeda
OBJECTIVE: The intestinal microbiota is involved in arthritis pathogenesis. Altered microbiota composition has been demonstrated in rheumatoid arthritis (RA) patients. However, it remains unclear how dysbiosis contributes to arthritis development. We investigated whether the altered composition of human intestinal microbiota in RA patients contributes to the development of arthritis. METHODS: We analyzed fecal microbiota of early RA patients and healthy controls by 16S rRNA-based deep sequencing...
June 22, 2016: Arthritis & Rheumatology
Larissa Lumi Watanabe Ishikawa, Priscila Maria Colavite, Thais Fernanda de Campos Fraga-Silva, Luiza Ayumi Nishiyama Mimura, Thais Graziela Donegá França, Sofia Fernanda Gonçalves Zorzella-Pezavento, Fernanda Chiuso-Minicucci, Larissa Doddi Marcolino, Camila Marques, Maura Rosane Valerio Ikoma, Alexandrina Sartori
This study was undertaken to evaluate the prophylactic potential of proteoglycan (PG) administration in experimental arthritis. Female BALB/c retired breeder mice received two (2xPG50 and 2xPG100 groups) or three (3xPG50 group) intraperitoneal doses of bovine PG (50 μg or 100 μg) every three days. A week later the animals were submitted to arthritis induction by immunization with three i.p. doses of bovine PG associated with dimethyldioctadecylammonium bromide adjuvant at intervals of 21 days. Disease severity was daily assessed after the third dose by score evaluation...
2016: Journal of Immunology Research
M R Hillen, F M Moret, Kmg van der Wurff-Jacobs, Trdj Radstake, C E Hack, Fpjg Lafeber, Jag van Roon
OBJECTIVES: Thymus and activation-regulated chemokine (TARC) attracts cells that express the C-C chemokine receptor type 4 (CCR4), including CD4 T cells. As expression of CCR4 is increased on peripheral T cells and intra-articular interleukin (IL)-17-producing cells in patients with rheumatoid arthritis (RA), we investigated whether TARC plays a role in the attraction of T cells to the synovial compartment. In addition, we assessed the role of classical dendritic cells (cDCs) in the production of TARC in RA...
June 2, 2016: Scandinavian Journal of Rheumatology
Ahmed S Elshikha, Yuanqing Lu, Mong-Jen Chen, Mohammad Akbar, Leilani Zeumer, Andrea Ritter, Hanaa Elghamry, Mahmoud A Mahdi, Laurence Morel, Sihong Song
Systemic lupus erythematosus (SLE) is an autoimmune disorder with a worldwide distribution and considerable mortality and morbidity. Although the pathogenesis of this disease remains elusive, over-reactive dendritic cells (DCs) play a critical role in the disease development. It has been shown that human alpha-1 antitrypsin (hAAT) has protective effects in type 1 diabetes and rheumatoid arthritis mouse models. In the present study, we tested the effect of AAT on DC differentiation and functions, as well as its protective effect in a lupus-prone mouse model...
2016: PloS One
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