TonEBP suppresses IL-10-mediated immunomodulation.
TonEBP suppresses IL-10-mediated immunomodulation.
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DOI：
10.1038/srep25726
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发表时间：
2016-05-10
影响因子：
4.6
通讯作者：
Kwon HM
中科院分区：
文献类型：
--
作者：
Choi SY;Lee HH;Lee JH;Ye BJ;Yoo EJ;Kang HJ;Jung GW;An SM;Lee-Kwon W;Chiong M;Lavandero S;Kwon HM
TonEBP是巨噬细胞M1表型的关键转录激活因子，其高表达与多种炎症性疾病相关。在炎症反应的进展过程中，M1至M2表型转换使巨噬细胞在控制炎症的起始和消退中发挥双重作用。在这里，我们报告说，在人类和小鼠M1巨噬细胞TonEBP抑制IL-10的表达和M2表型。TonEBP敲低通过增强染色质可及性和Sp1对其启动子的募集来促进IL-10基因的转录。通过中和抗体或siRNA介导的沉默的IL-10的拮抗作用消除了通过TonEBP敲低增强的M2基因表达。此外，TonEBP的药理学抑制导致IL-10和M2基因的类似上调。因此，TonEBP通过下调M1巨噬细胞中的IL-10来抑制M2表型。
TonEBP is a key transcriptional activator of M1 phenotype in macrophage, and its high expression is associated with many inflammatory diseases. During the progression of the inflammatory responses, the M1 to M2 phenotypic switch enables the dual role of macrophages in controlling the initiation and resolution of inflammation. Here we report that in human and mouse M1 macrophages TonEBP suppresses IL-10 expression and M2 phenotype. TonEBP knockdown promoted the transcription of the IL-10 gene by enhancing chromatin accessibility and Sp1 recruitment to its promoter. The enhanced expression of M2 genes by TonEBP knockdown was abrogated by antagonism of IL-10 by either neutralizing antibodies or siRNA-mediated silencing. In addition, pharmacological suppression of TonEBP leads to similar upregulation of IL-10 and M2 genes. Thus, TonEBP suppresses M2 phenotype via downregulation of the IL-10 in M1 macrophages.