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

Publication ,  Journal Article
Lin, X; Yang, J; Wang, J; Huang, H; Wang, H-X; Chen, P; Wang, S; Pan, Y; Qiu, Y-R; Taylor, GA; Vallance, BA; Gao, J; Zhong, X-P
Published in: Sci Rep
October 12, 2016

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

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Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

October 12, 2016

Volume

6

Start / End Page

34939

Location

England

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

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Lin, X., Yang, J., Wang, J., Huang, H., Wang, H.-X., Chen, P., … Zhong, X.-P. (2016). mTOR is critical for intestinal T-cell homeostasis and resistance to Citrobacter rodentium. Sci Rep, 6, 34939. https://doi.org/10.1038/srep34939
Lin, Xingguang, Jialong Yang, Jinli Wang, Hongxiang Huang, Hong-Xia Wang, Pengcheng Chen, Shang Wang, et al. “mTOR is critical for intestinal T-cell homeostasis and resistance to Citrobacter rodentium.Sci Rep 6 (October 12, 2016): 34939. https://doi.org/10.1038/srep34939.
Lin X, Yang J, Wang J, Huang H, Wang H-X, Chen P, et al. mTOR is critical for intestinal T-cell homeostasis and resistance to Citrobacter rodentium. Sci Rep. 2016 Oct 12;6:34939.
Lin, Xingguang, et al. “mTOR is critical for intestinal T-cell homeostasis and resistance to Citrobacter rodentium.Sci Rep, vol. 6, Oct. 2016, p. 34939. Pubmed, doi:10.1038/srep34939.
Lin X, Yang J, Wang J, Huang H, Wang H-X, Chen P, Wang S, Pan Y, Qiu Y-R, Taylor GA, Vallance BA, Gao J, Zhong X-P. mTOR is critical for intestinal T-cell homeostasis and resistance to Citrobacter rodentium. Sci Rep. 2016 Oct 12;6:34939.

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

October 12, 2016

Volume

6

Start / End Page

34939

Location

England

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