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Aryl hydrocarbon receptor AND multiple sclerosis

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https://www.readbyqxmd.com/read/27671624/laquinimod-arrests-experimental-autoimmune-encephalomyelitis-by-activating-the-aryl-hydrocarbon-receptor
#1
Joel Kaye, Victor Piryatinsky, Tal Birnberg, Tal Hingaly, Emanuel Raymond, Rina Kashi, Einat Amit-Romach, Ignacio S Caballero, Fadi Towfic, Mark A Ator, Efrat Rubinstein, Daphna Laifenfeld, Aric Orbach, Doron Shinar, Yael Marantz, Iris Grossman, Volker Knappertz, Michael R Hayden, Ralph Laufer
Laquinimod is an oral drug currently being evaluated for the treatment of relapsing, remitting, and primary progressive multiple sclerosis and Huntington's disease. Laquinimod exerts beneficial activities on both the peripheral immune system and the CNS with distinctive changes in CNS resident cell populations, especially astrocytes and microglia. Analysis of genome-wide expression data revealed activation of the aryl hydrocarbon receptor (AhR) pathway in laquinimod-treated mice. The AhR pathway modulates the differentiation and function of several cell populations, many of which play an important role in neuroinflammation...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27549171/er%C3%AE-dependent-direct-suppression-of-human-and-murine-th17-cells-and-treatment-of-established-central-nervous-system-autoimmunity-by-a-neurosteroid
#2
Maria Aggelakopoulou, Evangelia Kourepini, Nikolaos Paschalidis, Davina C M Simoes, Dimitra Kalavrizioti, Nikolaos Dimisianos, Panagiotis Papathanasopoulos, Athanasia Mouzaki, Vily Panoutsakopoulou
Multiple sclerosis (MS), an autoimmune disease of the CNS, is mediated by autoreactive Th cells. A previous study showed that the neurosteroid dehydroepiandrosterone (DHEA), when administered preclinically, could suppress progression of relapsing-remitting experimental autoimmune encephalomyelitis (EAE). However, the effects of DHEA on human or murine pathogenic immune cells, such as Th17, were unknown. In addition, effects of this neurosteroid on symptomatic disease, as well as the receptors involved, had not been investigated...
October 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27198196/gut-environment-induced-intraepithelial-autoreactive-cd4-t-cells-suppress-central-nervous-system-autoimmunity-via-lag-3
#3
Atsushi Kadowaki, Sachiko Miyake, Ryoko Saga, Asako Chiba, Hideki Mochizuki, Takashi Yamamura
The gut environment has been found to significantly influence autoimmune diseases such as multiple sclerosis; however, immune cell mechanisms are unclear. Here we show that the gut epithelium of myelin oligodendrocyte glycoprotein(35-55)-specific T-cell receptor transgenic mice contains environmental stimuli-induced intraepithelial lymphocytes (IELs) that inhibit experimental autoimmune encephalomyelitis on transfer. These cells express surface markers phenotypical of 'induced' IELs, have a TH17-like profile and infiltrate the central nervous system (CNS)...
May 20, 2016: Nature Communications
https://www.readbyqxmd.com/read/27183630/er%C3%AE-in-cd4-t-cells-is-crucial-for-ligand-mediated-suppression-of-central-nervous-system-autoimmunity
#4
Maria Aggelakopoulou, Evangelia Kourepini, Nikolaos Paschalidis, Vily Panoutsakopoulou
The development of therapies for multiple sclerosis targeting pathogenic T cell responses remains imperative. Previous studies have shown that estrogen receptor (ER) β ligands could inhibit experimental autoimmune encephalomyelitis. However, the effects of ERβ-specific ligands on human or murine pathogenic immune cells, such as Th17, were not investigated. In this article, we show that the synthetic ERβ-specific ligand 4-(2-phenyl-5,7-bis[trifluoromethyl]pyrazolo[1,5-a]pyrimidin-3-yl)phenol (PHTPP) reversed established paralysis and CNS inflammation, characterized by a dramatic suppression of pathogenic Th responses as well as induction of IL-10-producing regulatory CD4(+) T cell subsets in vivo...
June 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27158906/type-i-interferons-and-microbial-metabolites-of-tryptophan-modulate-astrocyte-activity-and-central-nervous-system-inflammation-via-the-aryl-hydrocarbon-receptor
#5
Veit Rothhammer, Ivan D Mascanfroni, Lukas Bunse, Maisa C Takenaka, Jessica E Kenison, Lior Mayo, Chun-Cheih Chao, Bonny Patel, Raymond Yan, Manon Blain, Jorge I Alvarez, Hania Kébir, Niroshana Anandasabapathy, Guillermo Izquierdo, Steffen Jung, Nikolaus Obholzer, Nathalie Pochet, Clary B Clish, Marco Prinz, Alexandre Prat, Jack Antel, Francisco J Quintana
Astrocytes have important roles in the central nervous system (CNS) during health and disease. Through genome-wide analyses we detected a transcriptional response to type I interferons (IFN-Is) in astrocytes during experimental CNS autoimmunity and also in CNS lesions from patients with multiple sclerosis (MS). IFN-I signaling in astrocytes reduces inflammation and experimental autoimmune encephalomyelitis (EAE) disease scores via the ligand-activated transcription factor aryl hydrocarbon receptor (AHR) and the suppressor of cytokine signaling 2 (SOCS2)...
June 2016: Nature Medicine
https://www.readbyqxmd.com/read/26822306/immunomodulation-by-subchronic-low-dose-2-3-7-8-tetrachlorodibenzo-p-dioxin-in-experimental-autoimmune-encephalomyelitis-in-the-absence-of-pertussis-toxin
#6
Eun-Ju Yang, John V Stokes, Evangel Kummari, Jeffrey Eells, Barbara L F Kaplan
Multiple sclerosis (MS) is an autoimmune neurodegenerative disorder, characterized by demyelination of neurons in the central nervous system. To investigate the pathogenicity of various T cell types in MS, especially IFN-γ- or IL-17-producing CD4(+ )cells (TH1 or TH17 cells, respectively), the mouse model, experimental autoimmune encephalomyelitis (EAE), is commonly used. One method by which EAE is induced is immunization with myelin oligodendrocyte glycoprotein (MOG) peptide (MOG35-55) followed by subsequent injections of pertussis toxin (PTX) as an adjuvant...
May 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/26601116/immunologic-and-mri-markers-of-the-therapeutic-effect-of-ifn-%C3%AE-1a-in-relapsing-remitting-ms
#7
Yazhong Tao, Xin Zhang, Robert Zivadinov, Michael G Dwyer, Cheryl Kennedy, Niels Bergsland, Deepa Ramasamy, Jacqueline Durfee, David Hojnacki, Brooke Hayward, Fernando Dangond, Bianca Weinstock-Guttman, Silva Markovic-Plese
OBJECTIVES: To assess potential roles of effector cells and immunologic markers in demyelinating CNS lesion formation, and their modulation by interferon β-1a (IFN-β-1a). METHODS: Twenty-three patients with relapsing-remitting multiple sclerosis (RRMS) received IFN-β-1a for 6 months. Immunologic marker results were correlated with brain MRI lesion volumes, and volumes of normal-appearing brain tissue (NABT) with decreasing or increasing voxel-wise magnetization transfer ratio (VW-MTR), suggestive of demyelination and remyelination, respectively...
December 2015: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/26341389/toxicity-of-teriflunomide-in-aryl-hydrocarbon-receptor-deficient-mice
#8
Chiara Redaelli, Ece Cazibe Gaffarogullari, Maik Brune, Caroline Pilz, Simon Becker, Jana Sonner, Andres Jäschke, Hermann-Josef Gröne, Wolfgang Wick, Michael Platten, Tobias Volker Lanz
The intracellular transcription factor aryl hydrocarbon receptor (AHR) is bound and activated by xenobiotics, thereby promoting their catabolism by inducing expression of cytochrome P450 oxidase (CYP) genes through binding xenobiotic response elements (XRE) in their promoter region. In addition, it is involved in several cellular pathways like cell proliferation, differentiation, regeneration, tumor invasiveness and immune responses. Several pharmaceutical compounds like benzimidazoles activate the AHR and induce their own metabolic degradation...
December 1, 2015: Biochemical Pharmacology
https://www.readbyqxmd.com/read/26276877/cutting-edge-ahr-is-a-molecular-target-of-calcitriol-in-human-t-cells
#9
Mariko Takami, Kotaro Fujimaki, Michael I Nishimura, Makio Iwashima
The immunoregulatory functions of vitamin D have been well documented in various immunological disorders, including multiple sclerosis, arthritis, and asthma. IL-10 is considered a chief effector molecule that promotes the vitamin D-induced immunosuppressive states of T cells and accessory cells. In this article, we demonstrate that the active form of vitamin D, 1,25-dihydroxyvitamin D3 (calcitriol), has a profound inhibitory effect on the development of human Th9, a CD4 T cell subset that is highly associated with asthma, in an IL-10-independent manner...
September 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/25938971/changing-the-face-of-kynurenines-and-neurotoxicity-therapeutic-considerations
#10
REVIEW
Zsuzsanna Bohár, József Toldi, Ferenc Fülöp, László Vécsei
Kynurenines are the products of tryptophan metabolism. Among them, kynurenine and kynurenic acid are generally thought to have neuroprotective properties, while 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid are considered neurotoxic. They participate in immunoregulation and inflammation and possess pro- or anti-excitotoxic properties, and their involvement in oxidative stress has also been suggested. Consequently, it is not surprising that kynurenines have been closely related to neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and multiple sclerosis...
April 29, 2015: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/25411844/fingolimod-increases-cd39-expressing-regulatory-t-cells-in-multiple-sclerosis-patients
#11
Nathalie Muls, Hong Anh Dang, Christian J M Sindic, Vincent van Pesch
BACKGROUND: Multiple sclerosis (MS) likely results from an imbalance between regulatory and inflammatory immune processes. CD39 is an ectoenzyme that cleaves ATP to AMP and has been suggested as a novel regulatory T cells (Treg) marker. As ATP has numerous proinflammatory effects, its degradation by CD39 has anti-inflammatory influence. The purpose of this study was to explore regulatory and inflammatory mechanisms activated in fingolimod treated MS patients. METHODS AND FINDINGS: Peripheral blood mononuclear cells (PBMCs) were isolated from relapsing-remitting MS patients before starting fingolimod and three months after therapy start...
2014: PloS One
https://www.readbyqxmd.com/read/23818645/aryl-hydrocarbon-receptor-mediated-induction-of-the-microrna-132-212-cluster-promotes-interleukin-17-producing-t-helper-cell-differentiation
#12
Taisuke Nakahama, Hamza Hanieh, Nam Trung Nguyen, Ichino Chinen, Barry Ripley, David Millrine, Soyoung Lee, Kishan Kumar Nyati, Praveen Kumar Dubey, Kamal Chowdhury, Yukio Kawahara, Tadamitsu Kishimoto
Aryl hydrocarbon receptor (AHR) plays critical roles in various autoimmune diseases such as multiple sclerosis by controlling interleukin-17 (IL-17)-producing T-helper (TH17) and regulatory T cells. Although various transcription factors and cytokines have been identified as key participants in TH17 generation, the role of microRNAs in this process is poorly understood. In this study, we found that expression of the microRNA (miR)-132/212 cluster is up-regulated by AHR activation under TH17-inducing, but not regulatory T-inducing conditions...
July 16, 2013: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/23696811/a-candidate-interactome-aggregate-analysis-of-genome-wide-association-data-in-multiple-sclerosis
#13
Rosella Mechelli, Renato Umeton, Claudia Policano, Viviana Annibali, Giulia Coarelli, Vito A G Ricigliano, Danila Vittori, Arianna Fornasiero, Maria Chiara Buscarinu, Silvia Romano, Marco Salvetti, Giovanni Ristori
Though difficult, the study of gene-environment interactions in multifactorial diseases is crucial for interpreting the relevance of non-heritable factors and prevents from overlooking genetic associations with small but measurable effects. We propose a "candidate interactome" (i.e. a group of genes whose products are known to physically interact with environmental factors that may be relevant for disease pathogenesis) analysis of genome-wide association data in multiple sclerosis. We looked for statistical enrichment of associations among interactomes that, at the current state of knowledge, may be representative of gene-environment interactions of potential, uncertain or unlikely relevance for multiple sclerosis pathogenesis: Epstein-Barr virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, HHV8-Kaposi sarcoma, H1N1-influenza, JC virus, human innate immunity interactome for type I interferon, autoimmune regulator, vitamin D receptor, aryl hydrocarbon receptor and a panel of proteins targeted by 70 innate immune-modulating viral open reading frames from 30 viral species...
2013: PloS One
https://www.readbyqxmd.com/read/23586923/indoles-mitigate-the-development-of-experimental-autoimmune-encephalomyelitis-by-induction-of-reciprocal-differentiation-of-regulatory-t-cells-and-th17-cells
#14
COMPARATIVE STUDY
Michael Rouse, Narendra P Singh, Prakash S Nagarkatti, Mitzi Nagarkatti
BACKGROUND AND PURPOSE: Dietary indole derivatives, indole-3-carbinol (I3C) and diindolylmethane (DIM), possess anti-cancer properties and exhibit the characteristics of aryl hydrocarbon receptor (AhR) ligands. Because AhR activation has recently been shown to regulate T cell differentiation, we tested the hypothesis that I3C and DIM may mediate anti-inflammatory properties by promoting regulatory T cell (T-regs) differentiation while inhibiting Th17 cells. EXPERIMENTAL APPROACH: We investigated the therapeutic efficacy of I3C and DIM against experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS)...
July 2013: British Journal of Pharmacology
https://www.readbyqxmd.com/read/23031832/inflammation-and-oxidative-stress-induced-by-cigarette-smoke-in-lewis-rat-brains
#15
A Khanna, M Guo, M Mehra, W Royal
Exposure to cigarette smoke has been associated with an increased risk of neurological diseases such as stroke, Alzheimer's disease and multiple sclerosis. In these studies, serum and brain sections from Lewis rats or those exposed to cigarette smoke and control rats were examined for evidence of increased inflammation and oxidative stress. Immunocytochemical staining of brain sections from CS-exposed rats showed increased expression of class II MHC and, in ELISA, levels of IFN-gamma and TNF-α were higher than for non-exposed rats...
January 15, 2013: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/22745170/nanoparticle-mediated-codelivery-of-myelin-antigen-and-a-tolerogenic-small-molecule-suppresses-experimental-autoimmune-encephalomyelitis
#16
Ada Yeste, Meghan Nadeau, Evan J Burns, Howard L Weiner, Francisco J Quintana
The immune response is normally controlled by regulatory T cells (Tregs). However, Treg deficits are found in autoimmune diseases, and therefore the induction of functional Tregs is considered a potential therapeutic approach for autoimmune disorders. The activation of the ligand-activated transcription factor aryl hydrocarbon receptor by 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) or other ligands induces dendritic cells (DCs) that promote FoxP3(+) Treg differentiation. Here we report the use of nanoparticles (NPs) to coadminister ITE and a T-cell epitope from myelin oligodendrocyte glycoprotein (MOG)(35)(-55) to promote the generation of Tregs by DCs...
July 10, 2012: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/21266776/liver-x-receptor-lxr-mediates-negative-regulation-of-mouse-and-human-th17-differentiation
#17
Guoliang Cui, Xia Qin, Lili Wu, Yuebo Zhang, Xiaoyan Sheng, Qiwen Yu, Hongguang Sheng, Beili Xi, Jingwu Z Zhang, Ying Qin Zang
Th17 cells are a subset of CD4+ T cells with an important role in clearing certain bacterial and fungal pathogens. However, they have also been implicated in autoimmune diseases such as multiple sclerosis. Exposure of naive CD4+ T cells to IL-6 and TGF-β leads to Th17 cell differentiation through a process in which many proteins have been implicated. We report here that ectopic expression of liver X receptor (LXR) inhibits Th17 polarization of mouse CD4+ T cells, while LXR deficiency promotes Th17 differentiation in vitro...
February 2011: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/20980695/the-inducible-costimulator-icos-is-critical-for-the-development-of-human-t-h-17-cells
#18
Chrystal M Paulos, Carmine Carpenito, Gabriela Plesa, Megan M Suhoski, Angel Varela-Rohena, Tatiana N Golovina, Richard G Carroll, James L Riley, Carl H June
Human T helper 17 (T(H)17) cells regulate host defense, autoimmunity, and tumor immunity. Although cytokines that control human T(H)17 cell development have been identified, the costimulatory molecules important for T(H)17 cell generation are unknown. Here, we found that the inducible costimulator (ICOS) was critical for the differentiation and expansion of human T(H)17 cells. Human cord blood contained a subset of CD161(+)CD4(+) T cells that were recent emigrants from the thymus, expressed ICOS constitutively, and were imprinted as T(H)17 cells through ICOS signaling...
October 27, 2010: Science Translational Medicine
https://www.readbyqxmd.com/read/18463656/community-corner-striking-the-balance-in-multiple-sclerosis
#19
Roland Martin, John O'Shea, Linda S Birnbaum, Robert Luebke
No abstract text is available yet for this article.
May 2008: Nature Medicine
https://www.readbyqxmd.com/read/17872969/resveratrol-trans-3-5-4-trihydroxystilbene-ameliorates-experimental-allergic-encephalomyelitis-primarily-via-induction-of-apoptosis-in-t-cells-involving-activation-of-aryl-hydrocarbon-receptor-and-estrogen-receptor
#20
COMPARATIVE STUDY
Narendra P Singh, Venkatesh L Hegde, Lorne J Hofseth, Mitzi Nagarkatti, Prakash Nagarkatti
Resveratrol (trans-3,5,4'-trihydroxystilbene), a polyphenolic compound found in plant products, including red grapes, exhibits anticancer, antioxidant, and anti-inflammatory properties. Using an animal model of multiple sclerosis (MS), we investigated the use of resveratrol for the treatment of autoimmune diseases. We observed that resveratrol treatment decreased the clinical symptoms and inflammatory responses in experimental allergic encephalomyelitis (EAE)-induced mice. Furthermore, we observed significant apoptosis in inflammatory cells in spinal cord of EAE-induced mice treated with resveratrol compared with the control mice...
December 2007: Molecular Pharmacology
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