Abstract
Bphs controls Bordetella pertussis toxin (PTX)-induced vasoactive amine sensitization elicited by histamine (VAASH) and has an established role in autoimmunity. We report that congenic mapping links Bphs to the histamine H1 receptor gene (Hrh1/H1R) and that H1R differs at three amino acid residues in VAASH-susceptible and -resistant mice. Hrh1-/- mice are protected from VAASH, which can be restored by genetic complementation with a susceptible Bphs/Hrh1 allele, and experimental allergic encephalomyelitis and autoimmune orchitis due to immune deviation. Thus, natural alleles of Hrh1 control both the autoimmune T cell and vascular responses regulated by histamine after PTX sensitization.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alleles
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Amino Acid Sequence
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Animals
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Autoimmune Diseases / etiology
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Autoimmune Diseases / genetics*
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Autoimmune Diseases / immunology
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Chromosome Mapping
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Cloning, Molecular
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Cytokines / biosynthesis
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Disease Susceptibility
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Encephalomyelitis, Autoimmune, Experimental / etiology
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Encephalomyelitis, Autoimmune, Experimental / genetics
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Encephalomyelitis, Autoimmune, Experimental / immunology
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Genetic Complementation Test
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Genetic Predisposition to Disease
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Histamine / pharmacology
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Mice
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Mice, Inbred C57BL
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Mice, Inbred CBA
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Mice, Inbred Strains
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Molecular Sequence Data
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Pertussis Toxin
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Polymorphism, Single Nucleotide
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Receptors, Histamine H1 / chemistry
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Receptors, Histamine H1 / genetics*
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Second Messenger Systems
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T-Lymphocytes / immunology
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Virulence Factors, Bordetella / toxicity
Substances
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Cytokines
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Receptors, Histamine H1
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Virulence Factors, Bordetella
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Histamine
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Pertussis Toxin