BOB.1/OBF.1控制TH1和TH2免疫反应的平衡。
BOB.1/OBF.1 controls the balance of TH1 and TH2 immune responses.
作者信息
Brunner Cornelia, Sindrilaru Anca, Girkontaite Irute, Fischer Klaus-Dieter, Sunderkötter Cord, Wirth Thomas
机构信息
Institute of Physiological Chemistry, University of Ulm, Ulm, Germany.
出版信息
EMBO J. 2007 Jul 11;26(13):3191-202. doi: 10.1038/sj.emboj.7601742. Epub 2007 Jun 14.
Abstract
BOB.1/OBF.1 is a transcriptional coactivator essential at several stages of B-cell development. In T cells, BOB.1/OBF.1 expression is inducible by co-stimulation. However, a defined role of BOB.1/OBF.1 for T-cell function had not been discovered so far. Here, we show that BOB.1/OBF.1 is critical for T helper cell function. BOB.1/OBF.1(-/-) mice showed imbalanced immune responses, resulting in increased susceptibility to Leishmania major infection. Functional analyses revealed specific defects in TH1 and TH2 cells. Whereas expression levels of TH1 cytokines were reduced, the secretion of TH2 cytokines was increased. BOB.1/OBF.1 directly contributes to the IFNgamma and IL2 promoter activities. In contrast, increased TH2 cytokine production is controlled indirectly, probably via the transcription factor PU.1, the expression of which is regulated by BOB.1/OBF.1. Thus, BOB.1/OBF.1 regulates the balance of TH1 versus TH2 mediated immunity.
摘要
BOB.1/OBF.1是一种转录共激活因子，在B细胞发育的多个阶段至关重要。在T细胞中，BOB.1/OBF.1的表达可通过共刺激诱导。然而，迄今为止尚未发现BOB.1/OBF.1在T细胞功能方面的明确作用。在此，我们表明BOB.1/OBF.1对辅助性T细胞功能至关重要。BOB.1/OBF.1基因敲除小鼠表现出免疫反应失衡，导致对杜氏利什曼原虫感染的易感性增加。功能分析揭示了TH1和TH2细胞中的特定缺陷。TH1细胞因子的表达水平降低，而TH2细胞因子的分泌增加。BOB.1/OBF.1直接促进IFNγ和IL2启动子的活性。相反，TH2细胞因子产生的增加可能是通过转录因子PU.1间接控制的，而PU.1的表达受BOB.1/OBF.1调节。因此，BOB.1/OBF.1调节TH1与TH2介导的免疫平衡。
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