mTOR is critical for intestinal T-cell homeostasis and resistance to Citrobacter rodentium

作者：Lin, Xingguang; Yang, Jialong; Wang, Jinli; Huang, Hongxiang; Wang, Hong-Xia; Chen, Pengcheng; Wang, Shang; Pan, Yun; Qiu, Yu-Rong; Taylor, Gregory A.; Vallance, Bruce A.; Gao, Jimin^*; Zhong, Xiao-Ping^*

来源：Scientific Reports, 2016, 6(1): 34939.

DOI：10.1038/srep34939

• TUMOR-SUPPRESSOR TSC1
• RAPAMYCIN COMPLEX 1
• MAMMALIAN TARGET
• IMMUNE HOMEOSTASIS
• MUCOSAL TISSUES
• DENDRITIC CELLS
• EFFECTOR
• DIFFERENTIATION
• EXPRESSION
• LYMPHOCYTES

T-cells play an important role in promoting mucosal immunity against pathogens, but the mechanistic basis for their homeostasis in the intestine is still poorly understood. We report here that T-cell-specific deletion of mTOR results in dramatically decreased CD4 and CD8 T-cell numbers in the lamina propria of both small and large intestines under both steady-state and inflammatory conditions. These defects result in defective host resistance against a murine enteropathogen, Citrobacter rodentium, leading to the death of the animals. We further demonstrated that mTOR deficiency reduces the generation of guthoming effector T-cells in both mesenteric lymph nodes and Peyer's patches without obviously affecting expression of gut-homing molecules on those effector T-cells. Using mice with T-cell-specific ablation of Raptor/mTORC1 or Rictor/mTORC2, we revealed that both mTORC1 and, to a lesser extent, mTORC2 contribute to both CD4 and CD8 T-cell accumulation in the gastrointestinal (GI) tract. Additionally, mTORC1 but not mTORC2 plays an important role regulating the proliferative renewal of both CD4 and CD8 T-cells in the intestines. Our data thus reveal that mTOR is crucial for T-cell accumulation in the GI tract and for establishing local adaptive immunity against pathogens.

• 出版日期2016-10-12
• 单位南方医科大学; 温州医科大学