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Rheumatoid arthritis and ido

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
Mi-Kyung Park, Hye-Jwa Oh, Yang-Mi Heo, Eun-Mi Park, Mi-La Cho, Ho-Youn Kim, Sung-Hwan Park
Indoleamine 2,3-dioxygenase (IDO) is a key negative regulator of immune responses and has been implicated in tumor tolerance, autoimmune disease and asthma. IDO was detected in the joint synovial tissue in the inflammatory microenvironment of rheumatoid arthritis (RA), but IDO expression in joint synovial tissue is not sufficient to overcome the inflamed synovial environment. This study aimed to unravel the mechanisms involving the failure to activate tolerogenic IDO in the inflamed joint. We demonstrate that both poly (I:C) and lipopolysaccharide (LPS) induce expression of IDO in synovial fibroblasts...
August 31, 2011: Experimental & Molecular Medicine
G C Prendergast, M Y Chang, L Mandik-Nayak, R Metz, A J Muller
Chronic inflammation underlies the basis for development and progression of cancers and a variety of other disorders, but what specifically defines its pathogenic nature remains largely undefined. Recent genetic and pharmacological studies in the mouse suggest that the immune modulatory enzyme indoleamine 2,3-dioxygenase (IDO), identified as an important mediator of immune escape in cancer, can also contribute to the development of pathology in the context of chronic inflammatory models of arthritis and allergic airway disease...
2011: Current Medicinal Chemistry
Katharina Kurz, Manfred Herold, Christiana Winkler, Werner Klotz, Elisabeth Russe, Dietmar Fuchs
In patients with rheumatoid arthritis (RA), overwhelming inflammatory activity and immune activation are indicated by elevated concentrations of immune activation markers such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and neopterin. Furthermore, accelerated tryptophan (Trp) degradation by the enzyme indoleamine 2,3-dioxygenase (IDO) is detectable in blood samples of patients by an increased kynurenine (Kyn) to Trp ratio (Kyn/Trp). This study comprises 22 patients (20 women, 2 men) with long-standing, moderate to severe RA, who were treated with a monoclonal tumor necrosis factor (TNF)-antibody (Adalimumab 40 mg subcutaneously every other week) in addition to their concomitant, but inadequate anti-rheumatic therapies...
May 2011: Autoimmunity
Janette Furuzawa-Carballeda, Guadalupe Lima, Juan Jakez-Ocampo, Luis Llorente
BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-degrading enzyme which suppresses T lymphocyte activity and induces Foxp3+ CD4+ regulatory T cells (Tregs) polarisation. The aim of this study was to evaluate the expression of IDO in freshly isolated peripheral cells as well as to enumerate Tregs and Th17 subpopulation in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients. MATERIALS AND METHODS: The percentage of IDO-expressing cells as well as Tregs and Th17 was evaluated in 14 active RA- (aRA), 13 inactive RA- (iRA), 7 aSLE-, 12 iSLE-treated patients and 11 healthy donors (controls)...
October 2011: European Journal of Clinical Investigation
Yanying Liu, Rong Mu, Shiyao Wang, Li Long, Xia Liu, Ru Li, Jian Sun, Jianping Guo, Xiaoping Zhang, Jing Guo, Ping Yu, Chunlei Li, Xiangyuan Liu, Zhenyu Huang, Dapeng Wang, Hu Li, Zhifeng Gu, Bing Liu, Zhanguo Li
INTRODUCTION: Rheumatoid arthritis (RA) is a T-cell-mediated systemic autoimmune disease, characterized by synovium inflammation and articular destruction. Bone marrow mesenchymal stem cells (MSCs) could be effective in the treatment of several autoimmune diseases. However, there has been thus far no report on umbilical cord (UC)-MSCs in the treatment of RA. Here, potential immunosuppressive effects of human UC-MSCs in RA were evaluated. METHODS: The effects of UC-MSCs on the responses of fibroblast-like synoviocytes (FLSs) and T cells in RA patients were explored...
2010: Arthritis Research & Therapy
Shih-Yao Chen, Chao-Liang Wu, Ming-Derg Lai, Chi-Chen Lin, Yi-Te Yo, I-Ming Jou, Che-Hsin Lee, Chia-Tse Weng, Ai-Li Shiau, Chrong-Reen Wang
Indoleamine 2,3-dioxygenase (IDO) has been known as an emerging therapeutic target in autoimmunity-related arthritis. The treatment responses of adenoviral vectors encoding IDO (AdIDO) gene therapy in rat collagen-induced arthritis (CIA) were examined in this study. The therapeutic effects on ankle circumference, articular index, and radiographic and histological scores were evaluated in AdIDO-injected ankle joints. We further determined CD4+ T-cell numbers and their apoptotic status, CD68(+) macrophage numbers, kynurenine (a downstream tryptophan metabolite) concentrations, interleukin-17 (IL-17) levels, and retinoic acid-related orphan receptor γt (RORγt) expression in synovial tissues of CIA rats receiving AdIDO treatment...
February 2011: Human Gene Therapy
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