首页> 外文期刊>Clinical immunology: The official journal of the Clinical Immunology Society >Tim-3 promotes intestinal homeostasis in DSS colitis by inhibiting M1 polarization of macrophages
【24h】

Tim-3 promotes intestinal homeostasis in DSS colitis by inhibiting M1 polarization of macrophages

机译:Tim-3通过抑制巨噬细胞的M1极化促进DSS结肠炎的肠道稳态

获取原文
获取原文并翻译 | 示例
           

摘要

Tim-3 is involved in the physiopathology of inflammatory bowel disease (IBD), but the underlying mechanism is unknown. Here, we demonstrated that, in mouse with DSS colitis, Tim-3 inhibited the polarization of pathogenic pro-inflammatory M1 macrophages, while Tim-3 downregulation or blockade resulted in an increased M1 response. Adoptive transfer of Tim-3-silenced macrophages worsened DSS colitis and enhanced inflammation, while Tim-3 overexpression attenuated DSS colitis by decreasing the M1 macrophage response. Co-culture of Tim-3-overexpressing macrophages with intestinal lymphocytes decreased the pro-inflammatory response. Tim-3 shaped intestinal macrophage polarization may be TLR-4 dependent since Tim-3 blockade failed to exacerbate colitis or increase M1 macrophage response in the TLR-4 KO model. Finally, Tim-3 signaling inhibited phosphorylation of IRF3, a TLR-4 downstream transcriptional factor regulating macrophage polarization. A better understanding of this pathway may shed new light on colitis pathogenesis and result in a new therapeutic strategy. (C) 2015 Elsevier Inc. All rights reserved.
机译:Tim-3参与了炎症性肠病(IBD)的生理病理,但其潜在机制尚不清楚。在这里,我们证明,在患有DSS结肠炎的小鼠中,Tim-3抑制了病原性促炎性M1巨噬细胞的极化,而Tim-3下调或阻断导致M1反应增加。 Tim-3沉默的巨噬细胞的过继转移使DSS结肠炎恶化并增强了炎症,而Tim-3的过表达通过降低M1巨噬细胞应答而减弱了DSS结肠炎。 Tim-3过表达的巨噬细胞与肠淋巴细胞的共培养降低了促炎反应。 Tim-3形状的肠道巨噬细胞极化可能是TLR-4依赖性的,因为在TLR-4 KO模型中,Tim-3阻断未能加剧结肠炎或增加M1巨噬细胞反应。最后,Tim-3信号传导抑制IRF3的磷酸化,IRF3是一种调节巨噬细胞极化的TLR-4下游转录因子。对该途径的更好理解可能为结肠炎的发病机理提供新的思路,并产生新的治疗策略。 (C)2015 Elsevier Inc.保留所有权利。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号