mTOR is critical for intestinal T-cell homeostasis and resistance to Citrobacter rodentium.
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 gut-homing 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.
Duke Scholars
Altmetric Attention Stats
Dimensions Citation Stats
Published In
DOI
EISSN
Publication Date
Volume
Start / End Page
Location
Related Subject Headings
- TOR Serine-Threonine Kinases
- T-Lymphocytes
- Regulatory-Associated Protein of mTOR
- Peyer's Patches
- Mucous Membrane
- Mice, Knockout
- Mice, Inbred C57BL
- Mice
- Intestines
- Inflammation
Citation
Published In
DOI
EISSN
Publication Date
Volume
Start / End Page
Location
Related Subject Headings
- TOR Serine-Threonine Kinases
- T-Lymphocytes
- Regulatory-Associated Protein of mTOR
- Peyer's Patches
- Mucous Membrane
- Mice, Knockout
- Mice, Inbred C57BL
- Mice
- Intestines
- Inflammation