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

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Wang, H-X; Shin, J; Wang, S; Gorentla, B; Lin, X; Gao, J; Qiu, Y-R; Zhong, X-P

Published Date

  • February 2016

Published In

Volume / Issue

  • 14 / 2

Start / End Page

  • e1002370 -

PubMed ID

  • 26889835

Pubmed Central ID

  • 26889835

Electronic International Standard Serial Number (EISSN)

  • 1545-7885

Digital Object Identifier (DOI)

  • 10.1371/journal.pbio.1002370

Language

  • eng

Conference Location

  • United States