Article ; Online: Activation of mTORC1 by LSECtin in macrophages directs intestinal repair in inflammatory bowel disease.
2020 Volume 11, Issue 10, Page(s) 918
Abstract: ... 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 ... mTOR, and increase the activation of mTORC1 induced by LSECtin in macrophages. Elevated mTORC1 ...
| 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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| MeSH term(s) | Animals ; Humans ; Inflammatory Bowel Diseases/genetics ; Lectins, C-Type/metabolism ; Macrophages/metabolism ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Mice ; Receptors, Virus/metabolism |
| Chemical Substances | LSECtin protein, mouse ; Lectins, C-Type ; Receptors, Virus ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) |
| Keywords | covid19 |
| Language | English |
| Publishing date | 2020-10-26 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2541626-1 |
| ISSN | 2041-4889 ; 2041-4889 |
| ISSN (online) | 2041-4889 |
| ISSN | 2041-4889 |
| DOI | 10.1038/s41419-020-03114-4 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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