Multiple elements of the allergic arm of the immune response modulate autoimmune demyelination.
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.
Pedotti
Rosetta
R
Department of Neurology and Neurological Science, Stanford University Medical Center, Stanford, CA 94305, USA.
DeVoss
Jason J
JJ
Youssef
Sawsan
S
Mitchell
Dennis
D
Wedemeyer
Jochen
J
Madanat
Rami
R
Garren
Hideki
H
Fontoura
Paulo
P
Tsai
Mindy
M
Galli
Stephen J
SJ
Sobel
Raymond A
RA
Steinman
Lawrence
L
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
D017931:DNA Primers