The IL15 +96522 A>T functional polymorphism is related to the differentiation of Th17 cells and the severity of Hashimoto's disease.
To clarify the association between the genetic producibility of IL-15, a pro-inflammatory cytokine, and the pathogenesis of autoimmune thyroid diseases (AITDs), we genotyped +96522 A>T and +82889 A>G polymorphisms in the IL15 gene using 127 patients with Hashimoto's disease (HD), including 55 patients with severe HD and 48 patients with mild HD; 130 patients with Graves' disease (GD), including 52 patients with intractable GD and 44 patients with GD in remission; and 79 healthy volunteers. Both the IL15 +96522 A allele and AA genotype were more frequent in patients with severe HD than in those with mild HD. The serum levels of IL-15 were higher in individuals with the IL15 +96522 AA genotype than in those with the T allele, and they were also higher in patients with severe HD than in those with mild HD. On the other hand, the mRNA levels of IL-15 were not significantly different among individuals with each genotype of both SNPs. After incubation with recombinant human IL-15, the proportions of Th17 cells in CD4+cells were increased, and those of Treg cells in CD4+cells were maintained. Our study indicates that the IL15 +96522A/C polymorphism correlates with the severity of HD, most likely by increasing Th17 cells.
Department of Biomedical Informatics, Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
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Arakawa
Department of Biomedical Informatics, Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
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Watanabe
Department of Biomedical Informatics, Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
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Takemura
Department of Laboratory Medicine, Osaka University Hospital, Suita, Osaka, Japan.
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Inoue
Department of Laboratory Medicine, Osaka University Hospital, Suita, Osaka, Japan.
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Hidaka
Department of Biomedical Informatics, Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
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Y
Iwatani
D000328:Adult; D000483:Alleles; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006111:Graves Disease / Q000235:genetics* / Q000473:pathology; D050031:Hashimoto Disease / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D006801:Humans; D019409:Interleukin-15 / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D058504:Th17 Cells / Q000276:immunology
C569274:IL15 protein, human; D019409:Interleukin-15