Effect of mTORC1 on intestinal group 3 innate lymphocytes function
10.3969/j.issn.1674-8115.2020.04.008
- VernacularTitle: 雷帕霉素靶蛋白复合物1对肠道3型固有淋巴细胞功能的影响
- Author:
Jian-Yue LIU
1
Author Information
1. Department of Immunology and Microbiology, Shanghai Jiao Tong University College of Basic Medical Sciences
- Publication Type:Journal Article
- Keywords:
Group 3 innate lymphoid cell (ILC3);
Interleukin 22 (IL-22);
Intestinal homeostasis;
Mechanistic target of rapamycin complex 1 (mTORC1);
Rapamycin
- From:
Journal of Shanghai Jiaotong University(Medical Science)
2020;40(4):464-471
- CountryChina
- Language:Chinese
-
Abstract:
Objective : To investigate the effect of mechanistic target of rapamycin complex 1 (mTORC1) on group 3 innate lymphoid cells (ILC3) function. Methods ¡¤ Intestinal lamina propria leukocytes (LPL) of C57BL/6 wild type mice were stimulated by rapamycin, the specific inhibitor of mTORC1 signaling pathway, in vitro, and then quantity and function of ILC3 were detected by flow cytometry. Next, purified ILC3 from mice intestinal LPL were sorted by flow cytometry. After the activation of ILC3 with IL-23, mRNA expression levels of Rorc (the gene encoding retinoic acid receptor related orphan receptor, i.e. RORγt), Il22 and Rptor (the gene encoding key component protein of mTORC1, i.e. Raptor) were detected by real-time qPCR. For further study, a genetically engineered mouse model specifically knocked out Raptor in ILC3 was constructed. Effects of mTORC1 loss on the quantity and function of ILC3 as well as gut structure were detected by flow cytometry, real-time qPCR and hematoxylin-eosin staining. Results ¡¤ The total ILC3 number had no change, but the secretion of IL-22 by ILC3 reduced after stim-ulation with rapamycin. Il22, Rorc and Rptor mRNA expression levels were upregulated simultaneously in ILC3 after activation with IL-23. In addition, there was no significant difference in the numbers and proportions of total ILC3 and ILC3 subsets as well as gut structure in Rap-tor-deficient mice, but the cytokine IL-22 secretion level of ILC3 significantly decreased in these mice. Conclusion ¡¤ Loss of mTORC1 func-tion inhibits ILC3 from secreting IL-22 but has no effect on the intestinal structure and intestinal ILC3 development, which reveals the positive regulation of mTORC1 signaling on intestinal ILC3 function.
