Influence of TBX21 T-1993C variant on autoimmune hepatitis development by Yin-Yang 1 binding

作     者：Wei Sun Hong-Yan Wu Song Chen 

作者机构：Institute of Infectious DiseasesSouthwest HospitalThe Third Military Medical University Nuclear Medicine Departmentthe First Affiliated HospitalChongqing Medical University 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2017年第23卷第48期

页      面：8500-8511页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：Supported by National Natural Science Foundation of China No.30972595 

主　　题：TBX21 Single nucleotide polymorphism Yin-Yang 1 T helper cells B cells Autoimmune hepatitis 

摘      要：AIM To investigated the mechanism of the association between the TBX21 T-1993 C promoter polymorphism and autoimmune hepatitis type 1(AIH-1) *** In vivo,In vivo,and reporter analyses were performed to determine the function of transcription factors binding to the T-1993 C element of the TBX21 promoter in human CD4+ T and B cell lines. Flow cytometry and quantitative real-time PCR were used to analyze T-box transcription factor(T-bet) and interferon-γ(IFN-γ) expressions in CD4+ T cells,B cells and monocytes from the peripheral blood of AIH-1 patients including 5-1993 TC and 15-1993 TT genotype carriers,and healthy controls including 10-1993 TC and 25-1993 TT genotype carriers. Furthermore,a range of biochemical indices was measured simultaneously in the blood of AIH-1 *** TBX21-1993 C allele created a strong Yin-Yang 1(YY1)-binding site and decreased transcriptional activity of TBX21 promoter in human CD4+ T and B *** levels of T-bet and IFN-γ were detected in the circulating CD4+ T cells and B cells of AIH-1 patients carrying the TBX21-1993 TT genotype compared with the patients carrying the-1993 TC genotype and controls with the-1993 TC genotype. T-bet expression levels of circulating T cells and B cells were positively correlated with AIH-1 disease activity. Knockdown of YY1 with si RNA caused increased expression of T-bet and IFN-γ in peripheral blood mononuclear cells in AIH-1 patients. CONCLUSION The repression of TBX21 expression by high-affinity binding of YY1 to the-1993 C allele may contribute to a decreased development of AIH-1 via suppression of type 1 immunity.