The mammalian target of rapamycin (mTOR) signaling pathway integrates 
environmental cues to regulate cell growth and survival through various 
mechanisms. However, how mTORC1 responds to acute inflammatory signals to 
regulate bowel regeneration is still obscure. In this study, we investigated the 
role of mTORC1 in acute inflammatory bowel disease. Inhibition of mTORC1 
activity by rapamycin treatment or haploinsufficiency of Rheb through genetic 
modification in mice impaired intestinal cell proliferation and induced cell 
apoptosis, leading to high mortality in dextran sodium sulfate- and 
2,4,6-trinitrobenzene sulfonic acid-induced colitis models. Through bone marrow 
transplantation, we found that mTORC1 in nonhematopoietic cells played a major 
role in protecting mice from colitis. Reactivation of mTORC1 activity by amino 
acids had a positive therapeutic effect in mTORC1-deficient Rheb(+/-) mice. 
Mechanistically, mTORC1 mediated IL-6-induced Stat3 activation in intestinal 
epithelial cells to stimulate the expression of downstream targets essential for 
cell proliferation and tissue regeneration. Therefore, mTORC1 signaling 
critically protects against inflammatory bowel disease through modulation of 
inflammation-induced Stat3 activity. As mTORC1 is an important therapeutic 
target for multiple diseases, our findings will have important implications for 
the clinical usage of mTORC1 inhibitors in patients with acute inflammatory 
bowel disease.