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

Rosetta Pedotti, Jason J. DeVoss, Sawsan Youssef, Dennis Mitchell, Jochen Wedemeyer, Rami Madanat, Hideki Garren, Paulo Fontoura, Mindy Tsai, Stephen J. Galli, Raymond A. Sobel, Lawrence Steinman

Research output: Contribution to journalArticle

112 Citations (Scopus)

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 ε receptor 1 (FcεRI), 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 FcγRIII or both FcγRIII and FcεRI. 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.

Original languageEnglish
Pages (from-to)1867-1872
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number4
DOIs
Publication statusPublished - Feb 18 2003

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Autoimmune Experimental Encephalomyelitis
Demyelinating Diseases
Autoimmunity
prostaglandin R2 D-isomerase
Tryptases
Histamine Receptors
Fc Receptors
Multiple Sclerosis
Myelin Proteolipid Protein
Pyrilamine
Th2 Cells
Immunoglobulin Genes
Th1 Cells
Brain
Response Elements
T-Cell Antigen Receptor
Hypersensitivity
Animal Models
Messenger RNA
Genes

ASJC Scopus subject areas

  • Genetics
  • General

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Multiple elements of the allergic arm of the immune response modulate autoimmune demyelination. / Pedotti, Rosetta; DeVoss, Jason J.; Youssef, Sawsan; Mitchell, Dennis; Wedemeyer, Jochen; Madanat, Rami; Garren, Hideki; Fontoura, Paulo; Tsai, Mindy; Galli, Stephen J.; Sobel, Raymond A.; Steinman, Lawrence.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 4, 18.02.2003, p. 1867-1872.

Research output: Contribution to journalArticle

Pedotti, R, DeVoss, JJ, Youssef, S, Mitchell, D, Wedemeyer, J, Madanat, R, Garren, H, Fontoura, P, Tsai, M, Galli, SJ, Sobel, RA & Steinman, L 2003, 'Multiple elements of the allergic arm of the immune response modulate autoimmune demyelination', Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 4, pp. 1867-1872. https://doi.org/10.1073/pnas.252777399
Pedotti, Rosetta ; DeVoss, Jason J. ; Youssef, Sawsan ; Mitchell, Dennis ; Wedemeyer, Jochen ; Madanat, Rami ; Garren, Hideki ; Fontoura, Paulo ; Tsai, Mindy ; Galli, Stephen J. ; Sobel, Raymond A. ; Steinman, Lawrence. / Multiple elements of the allergic arm of the immune response modulate autoimmune demyelination. In: Proceedings of the National Academy of Sciences of the United States of America. 2003 ; Vol. 100, No. 4. pp. 1867-1872.
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