title: mTOR is critical for intestinal T-cell homeostasis and resistance to Citrobacter rodentium.
abstract: 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.
authors.affiliation: Department of Pediatrics, Division of Allergy and Immunology, Duke University Medical Center, Durham, NC 27710, USA.|School of Laboratory Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Xingguang
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Pediatrics, Division of Allergy and Immunology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Jialong
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, Division of Allergy and Immunology, Duke University Medical Center, Durham, NC 27710, USA.|School of Laboratory Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Jinli
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Division of Allergy and Immunology, Duke University Medical Center, Durham, NC 27710, USA.|Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Pediatrics, Division of Allergy and Immunology, Duke University Medical Center, Durham, NC 27710, USA.|Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Division of Allergy and Immunology, Duke University Medical Center, Durham, NC 27710, USA.|School of Laboratory Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Division of Allergy and Immunology, Duke University Medical Center, Durham, NC 27710, USA.|School of Laboratory Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Shang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Division of Allergy and Immunology, Duke University Medical Center, Durham, NC 27710, USA.|School of Laboratory Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Yu-Rong
authors.initials: YR
authors.lastname: Qiu
authors.affiliation: Geriatric Research, Education, and Clinical Center, VA Medical Center, Durham, NC 27705, USA.|Department of Medicine, Division of Geriatrics, and Center for the Study of Aging and Human Development, Duke University Medical Center, Durham NC 27710, USA.|Department of Molecular Genetics and Microbiology Duke University Medical Center, Durham NC 27710, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Taylor
authors.affiliation: Division of Gastroenterology, Department of Pediatrics, Child and Family Research Institute and the University of British Columbia, Vancouver, British Columbia V6H 3V4, Canada.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Vallance
authors.affiliation: School of Laboratory Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Jimin
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Pediatrics, Division of Allergy and Immunology, Duke University Medical Center, Durham, NC 27710, USA.|Department of Immunology, Medical Center, Durham, NC 27710, USA.|Hematologic Malignancies and Cellular Therapies Program, Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Zhong
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D049109:Cell Proliferation; D044082:Citrobacter rodentium; D004756:Enterobacteriaceae Infections / Q000276:immunology*; D000069196:Gastrointestinal Microbiome; D041981:Gastrointestinal Tract / Q000378:metabolism / Q000382:microbiology; D006706:Homeostasis; D007249:Inflammation; D007422:Intestines / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009092:Mucous Membrane; D010581:Peyer's Patches / Q000276:immunology; D000076223:Regulatory-Associated Protein of mTOR / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000382:microbiology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D000076223:Regulatory-Associated Protein of mTOR; C540162:Rptor protein, mouse; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases