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Rheumatoid arthritis and ido

Zev Sthoeger, Amir Sharabi, Ilan Asher, Heidy Zinger, Rafael Segal, Gene Shearer, Ori Elkayam, Edna Mozes
Primary Sjogren's syndrome (pSS) is an autoimmune disease characterized by lymphocytic infiltration of exocrine glands. We investigated whether the tolerogenic peptide, hCDR1, that ameliorates lupus manifestations would have beneficial effects on pSS as well. The in vitro effects of hCDR1 on gene expression of pro-inflammatory cytokines and regulatory molecules were tested in peripheral blood mononuclear cells (PBMC) of 16 pSS patients. hCDR1, but not a control peptide, significantly reduced gene expression of IL-1β, TNF-α, MX-1 and BlyS and up-regulated immunosuppressive (TGF-β, FOXP3) molecules in PBMC of pSS patients...
May 3, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Benjar Issaranggun Na Ayuthaya, Vincent Everts, Prasit Pavasant
Interleukin 12 (IL-12) is an inflammatory cytokine that promotes the response of the immune system. This cytokine has been implicated as a potent stimulator of several diseases characterized by inflammatory-induced bone destruction, such as rheumatoid arthritis and periodontitis. Yet, the exact role of IL-12 in the development and progress of periodontitis has not been clarified. Several studies have demonstrated a positive correlation between the level of IL-12 and the severity of periodontal destruction. Deletion of IL-12 in mice with periodontitis significantly suppressed the level of bone destruction...
April 2018: European Journal of Oral Sciences
Yue Sun, Wei Deng, Genhong Yao, Weiwei Chen, Xiaojun Tang, Xuebing Feng, Liwei Lu, Lingyun Sun
Bone marrow mesenchymal stem cells (BMSC) have been shown to possess immunomodulatory activities, while its role in rheumatoid arthritis (RA) remains unknown. Citrullinated fibrinogen (cfb) has been considered as a specific autoantigen in RA pathogenesis. Our study aims to determine the role of cfb on immunomodulatory function of BMSC. We demonstrated the specific role of toll-like receptor 4 (TLR4)-NFκB pathway in the pro-inflammatory response of BMSC to cfb with increased production of interleukin (IL)-6, IL-8 and chemokine CC motif ligand 2 (CCL2)...
January 31, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Ari Polachek, Wilma Vree Egberts, Elizabeth Fireman, Ido Druckman, Moshe Stark, Daphna Paran, Ilana Kaufman, Irena Wigler, David Levartovsky, Dan Caspi, Ger J M Pruijn, Ori Elkayam
OBJECTIVE: The aim of this study was to evaluate the presence of autoantibodies to cyclic citrullinated synthetic peptides (ACPAs) in the sputum of patients with long-standing rheumatoid arthritis (RA). METHODS: Nineteen consecutive RA patients and 16 age- and sex-matched control subjects participated in this cross-sectional study. All underwent complete lung function tests and provided induced sputum. Antibodies to citrullinated (CitP) and the corresponding norleucine-containing (NorP) peptides in the sputum of the RA patients and control subjects, as well as in the serum of the RA patients, were determined by enzyme-linked immunosorbent assay...
December 1, 2017: Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases
Yuga Komaki, Akihiro Yamada, Fukiko Komaki, Praneeth Kudaravalli, Dejan Micic, Akio Ido, Atsushi Sakuraba
OBJECTIVE: To evaluate the efficacy and safety of biosimilars of anti-tumor necrosis factor (TNF)-α agents compared to their reference agents in immune mediated diseases. METHODS: Electronic databases were searched for randomized controlled trials (RCTs) assessing the efficacy and safety of biosimilars of anti-TNF-α agents compared to their reference agents in patients with various immune mediated diseases. The outcomes were the rates of clinical response and adverse events among patients treated with biosimilars compared to their reference agents...
May 2017: Journal of Autoimmunity
Fukiko Komaki, Yuga Komaki, Dejan Micic, Akio Ido, Atsushi Sakuraba
BACKGROUND: Immune mediated diseases such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), and inflammatory bowel disease (IBD) commonly affect young and adolescent females. Anti-tumor necrosis factor (TNF)-α agents are increasingly used to treat these conditions, but their safety during pregnancy remains unclear. OBJECTIVES: To evaluate the risk of pregnancy related outcomes in patients with various immune mediated diseases treated with anti-TNF-α agents...
January 2017: Journal of Autoimmunity
Masahiko Fukasawa, Yoshihiro Akazawa, Shigeru Kasugai, Koshi Mikami, Yoshimitsu Saito, Masatoshi Akutsu, Aibi Akashi, Kojiro Ido, Ichiro Maeda, Masahiro Hoshikawa, Izumi Koizuka
Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPD) comprise lymphoid proliferations or lymphomas that arise in patients treated with immunosuppressive drugs for autoimmune diseases, especially rheumatoid arthritis (RA) treated with methotrexate (MTX). MTX has been increasingly administered to patients with RA, resulting in methotrexate-associated lymphoproliferative disorder (MTX-LPD) in patients. We report herein on four cases of patients with RA, who diagnosed with head and neck region...
May 2016: Nihon Jibiinkoka Gakkai Kaiho
Jung-Yeon Lim, Keon-Il Im, Eun-Sol Lee, Nayoun Kim, Young-Sun Nam, Young-Woo Jeon, Seok-Goo Cho
Mesenchymal stem cells (MSCs) possess immunomodulatory properties and have potential, however, there have been conflicting reports regarding their effects in rheumatoid arthritis (RA), which causes inflammation and destruction of the joints. Through a comparative analysis of regulatory T (Treg) and IL-10-producing type 1 regulatory T (Tr1) cells, we hypothesized that Tr1 cells enhance the immunoregulatory functions of MSCs, and that a combinatorial approach to cell therapy may exert synergistic immunomodulatory effects in an experimental animal model of rheumatoid arthritis (RA)...
2016: Scientific Reports
Gregory Oxenkrug, Marieke van der Hart, Paul Summergrad
Experimental data suggested involvement of tryptophan (Trp) - kynurenine (Kyn) pathway (TKP) in mechanisms of autoimmune, type 1 (T1D), and metabolic, type 2 (T2D), diabetes. However, clinical evaluations of TKP metabolites were limited to T2D. We assessed Trp, Kyn and TKP metabolites: anthranilic (AA), kynurenic (KYNA) and xanthurenic (XA) acids, in plasma samples of fifteen T1D, thirty T2D patients and twenty eight non-diabetic subjects by HPLC-mass spectrometry. Trp concentrations were higher in T1D than in T2D and controls while Kyn concentrations were not changed suggesting down-regulation of indoleamine-2,3-dioxygenase (IDO), a rate-limiting enzyme of TKP, in T1D...
2015: Integrative Molecular Medicine
So-Youn Min, Mei Yan, Sang Bum Kim, Sneha Ravikumar, Seong-Ryuel Kwon, Kamala Vanarsa, Ho-Youn Kim, Laurie S Davis, Chandra Mohan
BACKGROUND: The activity of one of the major catechins in Green Tea, the polyphenol (-)-epigallocatechin-3-gallate (EGCG), has been shown to have a variety of health benefits. Recent studies suggest that EGCG can modulate both the innate and adaptive arms of the immune system. The goal of the current studies was to examine the immunomodulatory effects and mechanisms of action of EGCG on experimental arthritis in mice. METHODS: EGCG (10 mg/kg) was administered by oral gavage after CIA induction, while control mice were administered phosphate buffered saline (PBS)...
2015: Journal of Inflammation
Rui Liu, Xia Li, Zhuoya Zhang, Min Zhou, Yue Sun, Dinglei Su, Xuebing Feng, Xiang Gao, Songtao Shi, Wanjun Chen, Lingyun Sun
T follicular helper (Tfh) cells provide help for antigen-specific B cells. We have previously shown that Tfh cell frequency was increased and associated with auto-antibodies in patients with rheumatoid arthritis (RA), suggesting a possible involvement of Tfh cells in its pathogenesis. Mesenchymal stem cells (MSCs) represent a promising alternative cell therapy for RA by modulating T and B cell activation and proliferation. However, it remains unknown whether MSCs have immunoregulation on Tfh cells. In this paper, we have demonstrated that allogeneic MSCs could suppress Tfh cell differentiation in RA patients partly via the production of indoleamine 2,3-dioxygenase (IDO)...
2015: Scientific Reports
Cheng Zhao, Lu Zhang, Wei Kong, Jun Liang, Xinyun Xu, Hongyan Wu, Xuebing Feng, Bingzhu Hua, Hong Wang, Lingyun Sun
This study aimed to determine whether umbilical cord-derived mesenchymal stem cells (UCMSC) regulate Cadherin-11 (CDH11) expression by fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA). FLS were isolated from the synovium of RA and osteoarthritis (OA) patients. FLS from RA patients were cocultured with UCMSC in a transwell system. CDH11 mRNA levels in FLS were tested, and levels of soluble factors expressed by UCMSC, such as indoleamine 2,3-dioxygenase (IDO), hepatocyte growth factor (HGF), and interleukin- (IL-) 10, were determined...
2015: Journal of Immunology Research
Pablo Mancheño-Corvo, Ramón Menta, Borja del Río, Marcella Franquesa, Cristina Ramírez, Martin J Hoogduijn, Olga DelaRosa, Wilfried Dalemans, Eleuterio Lombardo
The immunomodulatory properties of mesenchymal stem/stromal cells (MSCs) make them an attractive therapeutic tool to treat chronic inflammatory diseases, such as rheumatoid arthritis or Crohn's disease. These indications are characterized by a chronic activation of immune cells that perpetuates the disease. In vitro, when adipose mesenchymal stem cells (ASCs) are cultured with T lymphocytes at the time of stimulation, their proliferation is inhibited. However, these experimental settings do not necessarily fit with what ASCs will face in inflammatory conditions in vivo, where ASCs will likely encounter and interact with already activated immune cells which might affect their immunomodulatory capacity...
September 15, 2015: Stem Cells and Development
Adam P Cribbs, Alan Kennedy, Henry Penn, Jordan E Read, Parisa Amjadi, Patricia Green, Khaja Syed, Szymon W Manka, Fionula M Brennan, Bernard Gregory, Richard O Williams
OBJECTIVE: Functionally impaired Treg cells expressing abnormally low levels of CTLA-4 have been well documented in rheumatoid arthritis (RA). However, the molecular defect underlying this reduced expression is unknown. The aims of this study were to assess the role of DNA methylation in regulating CTLA-4 expression in Treg cells isolated from RA patients and to elucidate the mechanism of their reduced suppressor function. METHODS: CTLA-4 expression in Treg cells from RA patients and healthy controls was measured by quantitative polymerase chain reaction (PCR) and flow cytometry...
September 2014: Arthritis & Rheumatology
Jiaxi Chen, Li Jun, Chen Shiyong, Hou Li, Ming Zhu, Bo Shen
Immune system activation is known to be involved in the progression of rheumatoid arthritis (RA). The aim of this work was to study the imbalance expressions of indoleamine 2,3-dioxygenase (IDO) and tryptophanyl-tRNA synthetase (TTS) with RA patients. Forty-nine RA patients and 49 healthy controls were studied. The expressions of IDO and TTS were analyzed by real-time quantitative polymerase chain reaction and flow cytometry in peripheral blood mononuclear cells. The expression of TTS mRNA increased significantly in RA patients when compared with healthy controls and correlated with erythrocyte sedimentation rate (r = 0...
February 2015: Clinical and Experimental Medicine
Lauren M F Merlo, Elizabeth Pigott, James B DuHadaway, Samantha Grabler, Richard Metz, George C Prendergast, Laura Mandik-Nayak
Rheumatoid arthritis and other autoimmune disorders are associated with altered activity of the immunomodulatory enzyme IDO. However, the precise contributions of IDO function to autoimmunity remain unclear. In this article, we examine the effect of two different IDO enzymes, IDO1 and IDO2, on the development of autoimmune arthritis in the KRN preclinical model of rheumatoid arthritis. We find that IDO2, not IDO1, is critical for arthritis development, providing direct evidence of separate in vivo functions for IDO1 and IDO2...
March 1, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
Richard O Williams
Indoleamine 2,3-dioxygenase (IDO) is the first and rate-limiting step along the kynurenine pathway and is thought to play a key role in immune homeostasis through depletion of tryptophan and accumulation of kynurenines. In this review we summarize recent research into the possibility of harnessing the IDO pathway for the therapy of rheumatoid arthritis. Inhibition of IDO activity, or knockout of the gene encoding IDO, was shown to cause an increase in the severity of collagen-induced arthritis, an animal model of rheumatoid arthritis...
2013: International Journal of Tryptophan Research: IJTR
P Filippini, N Del Papa, D Sambataro, A Del Bufalo, F Locatelli, S Rutella
The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) finely regulates both innate and adaptive immune responses through the degradation of the essential amino acid tryptophan into kynurenine and other downstream metabolites, which suppress effector T-cell function and promote the differentiation of regulatory T cells. A novel role for IDO1 as a signaling molecule and a modifier of innate inflammatory responses is now emerging. In particular, IDO1 can either support or antagonize inflammation in a context- and tissuedependent manner...
2012: Current Medicinal Chemistry
Maarten J C Leijs, Gerben M van Buul, Erik Lubberts, Pieter K Bos, Jan A N Verhaar, Martin J Hoogduijn, Gerjo J V M van Osch
BACKGROUND: In diseased joints, the catabolic environment results in progressive joint damage. Mesenchymal stem cells (MSCs) can have immunomodulatory effects by secreting anti-inflammatory factors. To exert these effects, MSCs need to be triggered by pro-inflammatory cytokines. To explore the potential of MSCs as a treatment for diseased joints, we studied the effect of synovial fluid (SF) from donors with different joint diseases and donors without joint pathology on the immunomodulatory capacities of human MSCs in vitro...
2012: Frontiers in Immunology
Lei Huang, Henrique P Lemos, Lingqian Li, MingHui Li, Phillip R Chandler, Babak Baban, Tracy L McGaha, Buvana Ravishankar, Jeffrey R Lee, David H Munn, Andrew L Mellor
Nanoparticles containing DNA complexed with the cationic polymer polyethylenimine are efficient vehicles to transduce DNA into cells and organisms. DNA/polyethylenimine nanoparticles (DNPs) also elicit rapid and systemic release of proinflammatory cytokines that promote antitumor immunity. In this study, we report that DNPs possess previously unrecognized immunomodulatory attributes due to rapid upregulation of IDO enzyme activity in lymphoid tissues of mice. IDO induction in response to DNP treatment caused dendritic cells and regulatory T cells (Tregs) to acquire potent regulatory phenotypes...
May 15, 2012: Journal of Immunology: Official Journal of the American Association of Immunologists
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