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mTORC1 in Thymic Epithelial Cells Is Critical for Thymopoiesis, T-Cell Generation, and Temporal Control of γδT17 Development and TCRγ/δ Recombination.

Publication ,  Journal Article
Wang, H-X; Shin, J; Wang, S; Gorentla, B; Lin, X; Gao, J; Qiu, Y-R; Zhong, X-P
Published in: PLoS Biol
February 2016

Thymus is crucial for generation of a diverse repertoire of T cells essential for adaptive immunity. Although thymic epithelial cells (TECs) are crucial for thymopoiesis and T cell generation, how TEC development and function are controlled is poorly understood. We report here that mTOR complex 1 (mTORC1) in TECs plays critical roles in thymopoiesis and thymus function. Acute deletion of mTORC1 in adult mice caused severe thymic involution. TEC-specific deficiency of mTORC1 (mTORC1KO) impaired TEC maturation and function such as decreased expression of thymotropic chemokines, decreased medullary TEC to cortical TEC ratios, and altered thymic architecture, leading to severe thymic atrophy, reduced recruitment of early thymic progenitors, and impaired development of virtually all T-cell lineages. Strikingly, temporal control of IL-17-producing γδT (γδT17) cell differentiation and TCRVγ/δ recombination in fetal thymus is lost in mTORC1KO thymus, leading to elevated γδT17 differentiation and rearranging of fetal specific TCRVγ/δ in adulthood. Thus, mTORC1 is central for TEC development/function and establishment of thymic environment for proper T cell development, and modulating mTORC1 activity can be a strategy for preventing thymic involution/atrophy.

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Published In

PLoS Biol

DOI

EISSN

1545-7885

Publication Date

February 2016

Volume

14

Issue

2

Start / End Page

e1002370

Location

United States

Related Subject Headings

  • Thymus Gland
  • TOR Serine-Threonine Kinases
  • T-Lymphocytes
  • Regulatory-Associated Protein of mTOR
  • Multiprotein Complexes
  • Mice, Inbred C57BL
  • Mechanistic Target of Rapamycin Complex 1
  • Developmental Biology
  • Chemokines
  • Cell Lineage
 

Citation

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Wang, H.-X., Shin, J., Wang, S., Gorentla, B., Lin, X., Gao, J., … Zhong, X.-P. (2016). mTORC1 in Thymic Epithelial Cells Is Critical for Thymopoiesis, T-Cell Generation, and Temporal Control of γδT17 Development and TCRγ/δ Recombination. PLoS Biol, 14(2), e1002370. https://doi.org/10.1371/journal.pbio.1002370
Wang, Hong-Xia, Jinwook Shin, Shang Wang, Balachandra Gorentla, Xingguang Lin, Jimin Gao, Yu-Rong Qiu, and Xiao-Ping Zhong. “mTORC1 in Thymic Epithelial Cells Is Critical for Thymopoiesis, T-Cell Generation, and Temporal Control of γδT17 Development and TCRγ/δ Recombination.PLoS Biol 14, no. 2 (February 2016): e1002370. https://doi.org/10.1371/journal.pbio.1002370.
Wang, Hong-Xia, et al. “mTORC1 in Thymic Epithelial Cells Is Critical for Thymopoiesis, T-Cell Generation, and Temporal Control of γδT17 Development and TCRγ/δ Recombination.PLoS Biol, vol. 14, no. 2, Feb. 2016, p. e1002370. Pubmed, doi:10.1371/journal.pbio.1002370.
Wang H-X, Shin J, Wang S, Gorentla B, Lin X, Gao J, Qiu Y-R, Zhong X-P. mTORC1 in Thymic Epithelial Cells Is Critical for Thymopoiesis, T-Cell Generation, and Temporal Control of γδT17 Development and TCRγ/δ Recombination. PLoS Biol. 2016 Feb;14(2):e1002370.
Journal cover image

Published In

PLoS Biol

DOI

EISSN

1545-7885

Publication Date

February 2016

Volume

14

Issue

2

Start / End Page

e1002370

Location

United States

Related Subject Headings

  • Thymus Gland
  • TOR Serine-Threonine Kinases
  • T-Lymphocytes
  • Regulatory-Associated Protein of mTOR
  • Multiprotein Complexes
  • Mice, Inbred C57BL
  • Mechanistic Target of Rapamycin Complex 1
  • Developmental Biology
  • Chemokines
  • Cell Lineage