Rabbit Anti-Human TBX21 (a.a. 1-328) Polyclonal antibody

Aim: Transcription factor T-bet is responsible for the differentiation of naive T lymphocytes, and its expression level is linked with different responses to some viral infections, including hepatitis B virus (HBV) infection. In this report we examine whether promoter polymorphisms of the TBX21 gene (encoding T-bet) are associated with susceptibility to HBV persistence or disease progression in chronic HBV carriers. Methods: Three previously reported promoter polymorphisms, T-1993C, T-1514C and G-1499A, were analyzed by polymerase chain reaction restriction fragment length polymorphism analysis. Two common polymorphisms, T-1993C and T-1514C, were selected for genotyping in 1074 chronic HBV carriers, 310 spontaneously recovered controls and 374 HBV naive controls. Of 1074 HBV carriers, 234 were considered to be asymptomatic carriers and 840 were found to have chronic progressive liver disease including cirrhosis and hepatocellular carcinoma. Haplotypes were constructed for each subject and associations with the susceptibility to persistent HBV infection were estimated by logistic regression. Results: The -1993C allele in the TBX21 promoter was significantly more common among chronic HBV carriers compared with recovered controls (chi(2) = 6.65, P = 0.01). In contrast, the frequency of TT haplotype at positions -1993/-1514, was significantly higher in recovered controls than chronic HBV carriers (P = 0.0027, odds ratio = 1.57; 95% confidence interval, 1.16-2.12). In HBV carriers, the TBX21 promoter polymorphisms were not linked to disease progression. Conclusion: The TBX21 promoter polymorphisms do not appear to be determinant of disease progression in Chinese HBV carriers. The T-1993C polymorphism in the TBX21 promoter influences susceptibility to persistent HBV infection.

T-bet is a key regulator for the lineage commitment in CD4(+) T helper (Th) 1 cells by activating the hallmark production of interferon-gamma. Previously, two single nucleotide polymorphisms (SNPs) in the TBX21 promoter, T-1993C and T-1514C, have been shown by statistic studies to associate with systemic lupus erythematosus (SLE). The effect of -1993 SNP on the Yin Yang 1 transcription factor-mediated promoter activity has been already indicated. This study aimed to investigate roles of the T-1514C SNP on TBX21 transcription and its functional effect by luciferase reporter, electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP) assay, and flow cytometric analysis of intracellular T-bet, IFN-gamma, and IL-4 expression in activated CD4(+) T cells. The TBX21 promoter carrying -1514C possessed significantly lower transcriptional activity than that of -1514T and was markedly downregulated by the overexpression of upstream stimulatory factor 1 (USF-1) when compared with the promoter carrying -1514T. EMSA indicated that the transcription factor USF-1 was bound to the -1514C allele probe with the affinity higher than that to the -1514T allele probe. ChIP assay suggested that USF-1 bound around -1514 of TBX21 genomic DNA in vivo in the human T cell line Jurkat with -1514C/T. The individuals carrying -1514C allele were determined to have significantly diminished expression of T-bet and IFN-gamma and increased IL-4 production in CD4(+) T cells compared with those of -1514T allele. The findings demonstrate that the T-1514C polymorphism affects TBX21 gene expression and Th1 cytokine production by binding USF-1 to the SNP site.