Differential effects of polymorphisms in the 5' flanking region of IL12RB2 on NK- and T-cell activity.
Single nucleotide polymorphisms (SNPs) in the 5' flanking region of IL12RB2 are frequently detected in lepromatous leprosy patients, and may be possible immunogenetic factors that reduce transcriptional activity of the IL-12Rbeta2 gene in Jurkat T cells. This study determined the functional effects of these SNPs on NK-cell activity, including IFN-gamma production and IL-12Rbeta2 gene expression. Reporter gene assays using the NK cell line NK3.3 revealed that transcriptional activities of the variant haplotypes were significantly higher in the NK cell line, in contrast to our previous results in Jurkat T cells. IFN-gamma production in activated T cells from donors was significantly lower than in cells from donors without the variant SNPs, while NK cells with these SNPs produced significantly higher amounts of IFN-gamma. These results suggest that these SNPs in IL12RB2 have differential effects on cellular activation of T cells and NK cells.
Ohyama
Hideki
H
Department of Pathology, Hyogo College of Medicine, Nishinomiya, Japan. ohyama@hyo-med.ac.jp
Kato-Kogoe
Nahoko
N
Nishimura
Fusanori
F
Takeuchi-Hatanaka
Kazu
K
Matsushita
Sho
S
Yamanegi
Koji
K
Yamada
Naoko
N
Hata
Masaki
M
Nakasho
Keiji
K
Terada
Nobuyuki
N
D024506:5' Flanking Region / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes / Q000235:genetics / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000276:immunology*; D015440:Leprosy, Lepromatous / Q000235:genetics / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics; D053707:Receptors, Interleukin-12 / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
C508439:IL12RB2 protein, human; D012333:RNA, Messenger; D053707:Receptors, Interleukin-12; D007371:Interferon-gamma