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 stimulatedrapamycin, the specific inhibitor of mTORC1 signaling pathway, in vitro, and then quantity and function of ILC3 were detectedflow cytometry. Next, purified ILC3 mice intestinal LPL were sortedflow cytometry. After the activation of ILC3 with IL-23, mRNA 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 detectedreal-time qPCR. For further study, a genetically engineered momodel 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 detectedflow cytometry, real-time qPCR and hematoxylin-eosin staining. Results · The total ILC3 number had no change, but the secretion of IL-22ILC3 reduced after stimulation with rapamycin. Il22, Rorc and Rptor mRNA 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 Raptor-deficient mice, but the cytokine IL-22 secretion level of ILC3 significantly decreased in these mice. Conclusion · Loss of mTORC1 function inhibits ILC3 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.

Key words: mechanistic target of rapamycin complex 1 (mTORC1), group 3 innate lymphoid cell (ILC3), interleukin 22 (IL-22), rapamycin, intestinal homeostasis