C-type lectin receptor LSECtin-mediated apoptotic cell clearance by macrophages directs intestinal repair in experimental colitis
C-type lectin receptor LSECtin-mediated apoptotic cell clearance by macrophages directs intestinal repair in experimental colitis
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C型凝集素受体LSECtin介导的巨噬细胞凋亡细胞清除指导实验性结肠炎的肠道修复
DOI：
10.1073/pnas.1804094115
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发表时间：
2018-10
期刊：
影响因子：
--
通讯作者：
Li Tang
中科院分区：
文献类型：
--
作者：
Zaopeng Yang;Qian Li;Xin Wang;Xuepei Jiang;Dianyuan Zhao;Xin Lin;Fuchu He;Li Tang
凋亡细胞的清除对于维持组织稳态至关重要，髓系c型凝集素受体（CLRs）可能在清除死亡细胞及其碎片中起重要作用。在这里，我们报道CLR成员LSECtin在参与尸体清除的巨噬细胞上表达。巨噬细胞通过LSECtin的吞噬过程对肠道愈合至关重要。由于肠上皮未修复，LSECtin的缺失促进了葡聚糖硫酸钠诱导的结肠炎。这些结果表明巨噬细胞清除尸体可以指导肠道再生。这些发现促进了对粘膜内如何维持稳态的理解。上皮屏障破坏是炎症性肠病（IBD）的主要原因；然而，肠上皮稳态的细胞和分子调控在很大程度上仍然不明确。在这里，我们表明巨噬细胞上的c型凝集素受体LSECtin （Clec4g）对葡聚糖硫酸钠诱导的结肠炎的保护是必需的。在机制上，LSECtin促进巨噬细胞清除凋亡细胞，并以吞噬依赖的方式诱导抗炎/组织修复因子的产生，从而刺激上皮细胞增殖。LSECtin的缺失导致结肠巨噬细胞吞噬缺陷，导致促溶因子产生异常和肠上皮修复受损。综上所述，我们的研究结果表明，巨噬细胞对lsectin依赖的尸体清除可以指导肠再生和损伤后粘膜屏障的维持。
Significance The clearance of apoptotic cells is critical for maintaining tissue homeostasis, and myeloid C-type lectin receptors (CLRs) may be prominently involved in the clearance of dying cells and their debris. Here, we report that the CLR member LSECtin is expressed on macrophages, which are engaged in corpse clearance. This engulfment progress by macrophages through LSECtin is critical for intestinal healing. Loss of LSECtin promotes dextran sulfate sodium-induced colitis due to unrepaired intestinal epithelium. These results indicate that corpse clearance by macrophages can direct intestinal regeneration. These findings advance understanding of how homeostasis is maintained within the mucosa. Epithelial barrier disruption is a major cause of inflammatory bowel disease (IBD); however, the cellular and molecular regulation of intestinal epithelial homeostasis remains largely undefined. Here, we show that the C-type lectin receptor LSECtin (Clec4g) on macrophages is required for protection against dextran sulfate sodium-induced colitis. Mechanistically, LSECtin promotes apoptotic cell clearance by macrophages and induces the production of antiinflammatory/tissue repair factors in an engulfment-dependent manner, which in turn stimulates epithelial cell proliferation. Deletion of LSECtin results in defective engulfment by colon macrophages, leading to aberrant proresolving factor production and impaired intestinal epithelium repair. Collectively, our findings suggest that LSECtin-dependent corpse clearance by macrophages can direct intestinal regeneration and maintenance of the mucosal barrier after injury.
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影响因子：
29.4
作者：
Tang L;Yang J;Liu W;Tang X;Chen J;Zhao D;Wang M;Xu F;Lu Y;Liu B;Sun Q;Zhang L;He F
通讯作者：
He F
通过髓样C型凝集素受体传感细胞死亡。
影响因子：
7
作者：
Sancho D;Reis e Sousa C
通讯作者：
Reis e Sousa C
影响因子：
64.8
作者：
Taniguchi, Koji;Wu, Li-Wha;Grivennikov, Sergei I.;de Jong, Petrus R.;Lian, Ian;Yu, Fa-Xing;Wang, Kepeng;Ho, Samuel B.;Boland, Brigid S.;Chang, John T.;Sandborn, William J.;Hardiman, Gary;Raz, Eyal;Maehara, Yoshihiko;Yoshimura, Akihiko;Zucman-Rossi, Jessica;Guan, Kun-Liang;Karin, Michael
通讯作者：
Karin, Michael
DOI：
10.1073/pnas.0803343106
发表时间：
2009-01-06
影响因子：
11.1
作者：
Seno, Hiroshi;Miyoshi, Hiroyuki;Stappenbeck, Thaddeus S.
通讯作者：
Stappenbeck, Thaddeus S.
影响因子：
3.9
作者：
A. Di Sabatino;R. Ciccocioppo;O. Luinetti;L. Ricevuti;R. Morera;M. Cifone;E. Solcia;G. Corazza
通讯作者：
A. Di Sabatino;R. Ciccocioppo;O. Luinetti;L. Ricevuti;R. Morera;M. Cifone;E. Solcia;G. Corazza