Chung Elaine Y, Liu Jianguo, Homma Yoichiro, Zhang Yunhua, Brendolan Andrea, Saggese Matilde, Han Jihong, Silverstein Roy, Selleri Licia, Ma Xiaojing
Department of Microbiology and Immunology, Medical College of Cornell University, New York, NY 10065, USA.
Immunity. 2007 Dec;27(6):952-64. doi: 10.1016/j.immuni.2007.11.014.
Production of interleukin (IL)-10, a major immunoregulatory cytokine, by phagocytes during clearance of apoptotic cells is critical to ensuring cellular homeostasis and suppression of autoimmunity. Little is known about the regulatory mechanisms in this fundamental process. We report that IL-10 production stimulated by apoptotic cells was regulated at the point of transcription in a manner dependent on p38 mitogen-activated protein kinase, partially on the scavenger receptor CD36, and required cell-cell contact but not phagocytosis. By using a reporter assay, we mapped the apoptotic-cell-response element (ACRE) in the human IL10 promoter and provide biochemical and physiological evidence that ACRE mediates the transcriptional activation of IL10 by pre-B cell leukemia transcription factor-1b and another Hox cofactor Pbx-regulating protein 1 in response to apoptotic cells. This study establishes a role of two developmentally critical factors (Pbx1 and Prep-1) in the regulation of homeostasis in the immune system.
在清除凋亡细胞过程中，吞噬细胞产生白细胞介素（IL）-10（一种主要的免疫调节细胞因子）对于确保细胞内稳态和抑制自身免疫至关重要。对于这一基本过程中的调节机制，人们了解甚少。我们报告称，凋亡细胞刺激产生的IL-10在转录水平受到调控，其方式依赖于p38丝裂原活化蛋白激酶，部分依赖于清道夫受体CD36，并且需要细胞间接触但不需要吞噬作用。通过使用报告基因检测，我们绘制了人类IL10启动子中的凋亡细胞反应元件（ACRE），并提供了生化和生理学证据，表明ACRE介导前B细胞白血病转录因子-1b和另一种Hox辅因子Pbx调节蛋白1对凋亡细胞的反应，从而介导IL10的转录激活。本研究确立了两个在发育中起关键作用的因子（Pbx1和Prep-1）在免疫系统稳态调节中的作用。
