title: Multiple elements of the allergic arm of the immune response modulate autoimmune demyelination.
abstract: Analysis of mRNA from multiple sclerosis lesions revealed increased amounts of transcripts for several genes encoding molecules traditionally associated with allergic responses, including prostaglandin D synthase, histamine receptor type 1 (H1R), platelet activating factor receptor, Ig Fc epsilon receptor 1 (Fc epsilon RI), and tryptase. We now demonstrate that, in the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), mediated by T helper 1 (Th1) T cells, histamine receptor 1 and 2 (H1R and H2R) are present on inflammatory cells in brain lesions. Th1 cells reactive to myelin proteolipid protein expressed more H1R and less H2R than Th2 cells. Pyrilamine, an H1R antagonist, blocked EAE, and the platelet activating factor receptor antagonist CV6209 reduced the severity of EAE. EAE severity was also decreased in mice with disruption of the genes encoding Ig Fc gamma RIII or both Fc gamma RIII and Fc epsilon RI. Prostaglandin D synthase and tryptase transcripts were elevated in EAE brain. Taken together, these data reveal extensive involvement of elements of the immune response associated with allergy in autoimmune demyelination. The pathogenesis of demyelination must now be viewed as encompassing elements of both Th1 responses and "allergic" responses.
authors.affiliation: Department of Neurology and Neurological Science, Stanford University Medical Center, Stanford, CA 94305, USA.
authors.forename: Rosetta
authors.initials: R
authors.lastname: Pedotti
authors.forename: Jason J
authors.initials: JJ
authors.lastname: DeVoss
authors.forename: Sawsan
authors.initials: S
authors.lastname: Youssef
authors.forename: Dennis
authors.initials: D
authors.lastname: Mitchell
authors.forename: Jochen
authors.initials: J
authors.lastname: Wedemeyer
authors.forename: Rami
authors.initials: R
authors.lastname: Madanat
authors.forename: Hideki
authors.initials: H
authors.lastname: Garren
authors.forename: Paulo
authors.initials: P
authors.lastname: Fontoura
authors.forename: Mindy
authors.initials: M
authors.lastname: Tsai
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Galli
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Sobel
authors.forename: Lawrence
authors.initials: L
authors.lastname: Steinman
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D020869:Gene Expression Profiling; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology*; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009103:Multiple Sclerosis / Q000276:immunology*; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D017931:DNA Primers