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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
Karen Put, Ellen Brisse, Anneleen Avau, Maya Imbrechts, Tania Mitera, Rik Janssens, Paul Proost, Francesca Fallarino, Carine H Wouters, Patrick Matthys
OBJECTIVES: Indoleamine 2,3-dioxygenase-1 (IDO1) is an immune-modulatory enzyme that catalyzes the degradation of tryptophan (Trp) to kynurenine (Kyn) and is strongly induced by interferon (IFN)-γ. We previously reported highly increased levels of IFN-γ and corresponding IDO activity in patients with hemophagocytic lymphohistiocytosis (HLH), a hyper-inflammatory syndrome. On the other hand, IFN-γ and IDO were low in patients with systemic juvenile idiopathic arthritis (sJIA), an autoinflammatory syndrome...
2016: PloS One
Patricia Luz-Crawford, Maria J Torres, Daniele Noël, Ainoa Fernandez, Karine Toupet, Francisca Alcayaga-Miranda, Gautier Tejedor, Christian Jorgensen, Sebastian E Illanes, Fernando E Figueroa, Farida Djouad, Maroun Khoury
Recently, a noninvasive and highly proliferative stem cell population from menstrual blood called MenSCs has been identified. Despite their use in clinical studies, their immunomodulatory properties have not yet been investigated. In this context, we studied the immunosuppressive properties of MenSCs in comparison with the well-characterized bone marrow derived-MSCs (BM-MSCs). Using an in vitro proliferation assays, we showed that MenSCs displayed a lower suppressive effect on peripheral blood mononuclear cells and in particular on the proinflammatory CD4(+) IFN-γ(+) and CD8(+) IFNγ(+) cells than BM-MSCs...
February 2016: Stem Cells
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
Rodrigo Arreola, Enrique Becerril-Villanueva, Carlos Cruz-Fuentes, Marco Antonio Velasco-Velázquez, María Eugenia Garcés-Alvarez, Gabriela Hurtado-Alvarado, Saray Quintero-Fabian, Lenin Pavón
Serotonin (5-HT) induces concentration-dependent metabolic effects in diverse cell types, including neurons, entherochromaffin cells, adipocytes, pancreatic beta-cells, fibroblasts, smooth muscle cells, epithelial cells, and leukocytes. Three classes of genes regulating 5-HT function are constitutively expressed or induced in these cells: (a) membrane proteins that regulate the response to 5-HT, such as SERT, 5HTR-GPCR, and the 5HT3-ion channels; (b) downstream signaling transduction proteins; and (c) enzymes controlling 5-HT metabolism, such as IDO and MAO, which can generate biologically active catabolites, including melatonin, kynurenines, and kynurenamines...
2015: Journal of Immunology Research
Lingling Zhang, Jingjing Fu, Kangliang Sheng, Ying Li, Shanshan Song, Peipei Li, Shasha Song, Qingtong Wang, Jingyu Chen, Jianhua Yu, Wei Wei
Tolerogenic dendritic cells (DCs) are well-known to show an immunosuppressive function. In this study we determine the therapeutic effects and potential mechanisms of transferred bone marrow (BM) CD11b(+)F4/80(+) DCs on collagen-induced arthritis (CIA) in mice. Murine BM CD11b(+)F4/80(+) DCs were generated under the stimulation of GM-CSF and IL-4, and the function of BM CD11b(+) F4/80(+) DCs was identified by measuring the levels of IL-10, TGF-beta and indoleamine 2,3-dioxygenase (IDO). BM CD11b(+)F4/80(+) DCs were transferred to CIA mice by intravenous injections...
March 2015: International Immunopharmacology
Jie Yang, Yiming Yang, Huahua Fan, Hejian Zou
TGF-β-induced regulatory T cells (iTregs) retain Foxp3 expression and immune-suppressive activity in collagen-induced arthritis (CIA). However, the mechanisms whereby transferred iTregs suppress immune responses, particularly the interplay between iTregs and dendritic cells (DCs) in vivo, remain incompletely understood. In this study, we found that after treatment with iTregs, splenic CD11c(+)DCs, termed "DCiTreg," expressed tolerogenic phenotypes, secreted high levels of IL-10, TGF-β, and IDO, and showed potent immunosuppressive activity in vitro...
2014: Journal of Immunology Research
Nam Trung Nguyen, Taisuke Nakahama, Duc Hoang Le, Le Van Son, Ha Hoang Chu, Tadamitsu Kishimoto
Aryl hydrocarbon receptor (AHR) is thought to be a crucial factor in the regulation of immune responses. Many AHR-mediated immunoregulatory mechanisms have been discovered, and this knowledge may enhance our understanding of the molecular pathogenesis of autoimmune inflammatory syndromes such as collagen-induced arthritis, experimental autoimmune encephalomyelitis, and experimental colitis. Recent findings have elucidated the critical link between AHR and indoleamine 2,3-dioxygenase (IDO) in the development of regulatory T cells and Th17 cells, which are key factors in a variety of human autoimmune diseases...
2014: Frontiers in Immunology
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
Mi-Kyung Park, Jin-Sil Park, Eun-Mi Park, Mi-Ae Lim, Sung-Min Kim, Dong-Gun Lee, Seung-Ye Baek, Eun-Ji Yang, Jung-Won Woo, Jennifer Lee, Seung-Ki Kwok, Ho-Youn Kim, Mi-La Cho, Sung-Hwan Park
OBJECTIVE: The small molecule halofuginone has been shown to inhibit fibrosis, angiogenesis, and tumor progression. This study was undertaken to evaluate the effects of halofuginone in preventing autoimmune arthritis in mice. METHODS: The effects of halofuginone on joint diseases were assessed by clinical scoring and histologic analysis. Protein expression levels were confirmed by immunohistochemistry, enzyme-linked immunosorbent assay, flow cytometry, and/or Western blotting...
May 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
Jingjing Fu, Lingling Zhang, Shanshan Song, Kangliang Sheng, Ying Li, Peipei Li, Shasha Song, Qingtong Wang, Jianhong Chu, Wei Wei
OBJECTIVE: To explore the effect of bone marrow-derived CD11b(+)F4/80(+) immature dendritic cells (BM CD11b(+)F4/80(+)iDC) on the balance between pro-inflammatory and anti-inflammatory cytokines in DBA/1 mice with collagen-induced arthritis (CIA). METHODS: BM CD11b(+)F4/80(+)iDC were induced with rmGM-CSF and rmIL-4, and were identified by the expressions of toll-like receptor 2 (TLR-2), indoleamine 2,3-deoxygenase (IDO), interleukin (IL)-10, transforming growth factor (TGF)-β1 and mixed leukocyte reaction (MLR)...
May 2014: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Mi-Kyung Park, Jin-Sil Park, Eun-Mi Park, Mi-Ae Lim, Sung-Min Kim, Dong-Gun Lee, Seung-Ye Baek, Eun-Ji Yang, Jung-Won Woo, Jennifer Lee, Seung-Ki Kwok, Ho-Youn Kim, Mi-La Cho, Sung-Hwan Park
Objective. The small molecule halofuginone (HF) has been shown to inhibit fibrosis, angiogenesis, and tumor progression. The objective of this study was to evaluate the effects of HF in preventing autoimmune arthritis in mice. Methods. The effects of HF on joint diseases were assessed by clinical scoring and histological analysis. Protein expression levels were confirmed by immunohistochemistry, ELISA, flow cytometry, and/or Western blotting. The mRNA expression levels of various molecules were determined by real-time PCR...
December 10, 2013: Arthritis and Rheumatism
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
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