title: Mutations of the IL-12 receptor beta2 chain gene in atopic subjects.
abstract: Interleukin-12(IL-12) promotes cell-mediated Th1 responses and production of IFN-gamma that downregulates IgE production. The signal of IL-12 is transduced through the IL-12 receptor (IL-12R) and Stat4. Twenty-four of 75 atopic individuals with high levels of IgE showed insufficient IFN-gamma production by peripheral blood mononuclear cells (PBMCs) following stimulation with IL-12 but not that with phytohemagglutinin (PHA). Interestingly, 10 of the above 24 subjects were found to be heterozygous for truncated (2496 del 91) or missense (1577 A to G and 2799 A to G) mutations of IL-12R beta2 chain gene (IL-12R beta2). Insufficient phosphorylation of Stat4 was also demonstrated in these 10 individuals. This is the first report showing that reduced IFN-gamma production following IL-12 stimulation is associated with the heterozygous IL-12R beta2 mutations in atopic subjects.
authors.affiliation: Department of Pediatrics, Gifu University School of Medicine, 40 Tsukasa-machi, Gifu, 500-8705, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Matsui
authors.forename: H
authors.initials: H
authors.lastname: Kaneko
authors.forename: T
authors.initials: T
authors.lastname: Fukao
authors.forename: T
authors.initials: T
authors.lastname: Teramoto
authors.forename: R
authors.initials: R
authors.lastname: Inoue
authors.forename: M
authors.initials: M
authors.lastname: Watanabe
authors.forename: K
authors.initials: K
authors.lastname: Kasahara
authors.forename: N
authors.initials: N
authors.lastname: Kondo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D007223:Infant; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000494:pharmacology; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D009154:Mutation; D010766:Phosphorylation; D018123:Receptors, Interleukin / Q000235:genetics*; D053707:Receptors, Interleukin-12; D050797:STAT4 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C508439:IL12RB2 protein, human; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D015534:Trans-Activators; D018664:Interleukin-12; D007073:Immunoglobulin E; D007371:Interferon-gamma