RGD Reference Report - Multiple elements of the allergic arm of the immune response modulate autoimmune demyelination. - Rat Genome Database

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Multiple elements of the allergic arm of the immune response modulate autoimmune demyelination.

Authors: Pedotti, R  DeVoss, JJ  Youssef, S  Mitchell, D  Wedemeyer, J  Madanat, R  Garren, H  Fontoura, P  Tsai, M  Galli, SJ  Sobel, RA  Steinman, L 
Citation: Pedotti R, etal., Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1867-72. Epub 2003 Feb 7.
RGD ID: 5508383
Pubmed: PMID:12576552   (View Abstract at PubMed)
PMCID: PMC149925   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.252777399   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Autoimmune Encephalomyelitis  ISOFcgr3 (Mus musculus)5508383; 5508383 RGD 
Experimental Autoimmune Encephalomyelitis  IMP 5508383 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Fcgr2a  (Fc gamma receptor 2A)

Genes (Mus musculus)
Fcgr3  (Fc receptor, IgG, low affinity III)

Genes (Homo sapiens)
FCGR2A  (Fc gamma receptor IIa)

Objects referenced in this article
Gene FCGR3A Fc gamma receptor IIIa Homo sapiens
Gene Fcgr4 Fc receptor, IgG, low affinity IV Mus musculus
Gene Fcgr3a Fc gamma receptor 3A Rattus norvegicus

Additional Information