炎症性肠病
mTORC1型
疾病
炎症性肠病
炎症
结肠炎
免疫学
医学
癌症研究
微生物学
生物
信号转导
细胞生物学
病理
PI3K/AKT/mTOR通路
作者
Qian Li,Hanxing Cheng,Yuanping Liu,Xiaowen Wang,Fuchu He,Li Tang
标识
DOI:10.1038/s41419-020-03114-4
摘要
Abstract Damage to intestinal epithelial cells and the induction of cellular apoptosis are characteristics of inflammatory bowel disease. The C-type lectin receptor family member LSECtin promotes apoptotic cell clearance by macrophages and induces the production of anti-inflammatory/tissue growth factors, which direct intestinal repair in experimental colitis. However, the mechanisms by which the phagocytosis of apoptotic cells triggers the pro-repair function of macrophages remain largely undefined. Here, using immunoprecipitation in combination with mass spectrometry to identify LSECtin-interacting proteins, we found that LSECtin interacted with mTOR, exhibiting a role in activating mTORC1. Mechanistically, apoptotic cells enhance the interaction between LSECtin and mTOR, and increase the activation of mTORC1 induced by LSECtin in macrophages. Elevated mTORC1 signaling triggers macrophages to produce anti-inflammatory/tissue growth factors that contribute to the proliferation of epithelial cells and promote the reestablishment of tissue homeostasis. Collectively, our findings suggest that LSECtin-dependent apoptotic cell clearance by macrophages activates mTORC1, and thus contributes to intestinal regeneration and the remission of colitis.
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