title: Immunomodulation By Subchronic Low Dose 2,3,7,8-Tetrachlorodibenzo-p-Dioxin in Experimental Autoimmune Encephalomyelitis in the Absence of Pertussis Toxin.
abstract: 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. We have an interest in the mechanisms by which EAE occurs in the absence of PTX because it induces a milder disease state more consistent with autoimmune disease onset and PTX inactivates Gi/o protein-coupled receptors, many of which contribute to immune homeostasis. Another receptor that plays a role in immune homeostasis is the aryl hydrocarbon receptor (AHR). In fact, the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been shown to attenuate EAE pathogenesis by affecting CD4(+ )T and regulatory T (Treg) cells in an AHR-dependent manner. However, many of these studies have been conducted with an acute high dose TCDD. Thus, the goal of this work was to investigate the modulation of MOG-specific immune responses with subchronic low dose TCDD (0.1-1.0 μg/kg/d for 12 days) in EAE without PTX. The results demonstrate that subchronic, low dose exposure of TCDD attenuates the immune responses in EAE development in the absence of PTX, which is due in part to suppression of MOG-specific IL-17A and IFN-γ responses.
authors.affiliation: Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi 39762.
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Yang
authors.affiliation: Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi 39762.
authors.forename: John V
authors.initials: JV
authors.lastname: Stokes
authors.affiliation: Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi 39762.
authors.forename: Evangel
authors.initials: E
authors.lastname: Kummari
authors.affiliation: Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi 39762.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Eells
authors.affiliation: Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi 39762 barbara.kaplan@msstate.edu.
authors.forename: Barbara L F
authors.initials: BL
authors.lastname: Kaplan
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000819:agonists / Q000378:metabolism; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism*; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D019363:Cytochrome P-450 CYP1A1; D007166:Immunosuppressive Agents; D007371:Interferon-gamma; D020381:Interleukin-17; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; C484722:Ahr protein, mouse; C000611649:IFNG protein, mouse; C098680:Il17a protein, mouse; C445081:myelin oligodendrocyte glycoprotein (35-55)
keywords: EAE; IFN-γ; IL-17; TCDD; Tregs; immunomodulation.
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