ArticleAutophagy2018
MTOR signaling is essential for the development of thymic epithelial cells and the induction of central immune tolerance.
Article in Autophagy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 32 citations in OpenAlex.
- Paracrine FGF21 dynamically modulates mTOR signaling to regulate thymus function across the lifespan.Nature aging · 2025Article
- Metabolic Signaling as a Driver of T Cell Aging.Immune network · 2025Review
- The mouse multi-organ proteome from infancy to adulthood.Nature communications · 2024Article
- Autophagy and proteasomes in thymic epithelial cells: essential bulk protein degradation systems for immune homeostasis maintenance.Frontiers in immunology · 2024Review
- Activating Wnt/β-catenin signaling by autophagic degradation of APC contributes to the osteoblast differentiation effect of soy isoflavone on osteoporotic mesenchymal stem cells.Acta pharmacologica Sinica · 2023Article
- The proprotein convertase furin regulates the development of thymic epithelial cells to ensure central immune tolerance.iScience · 2022Article
- A Spontaneous H2-Aa Point Mutation Impairs MHC II Synthesis and CD4Frontiers in immunology · 2022Article
- Sirolimus treatment induces dose-dependent involution of the thymus with elevated cellular respiration in BALB/c mice.American journal of translational research · 2022Article
- Epigenetic modifications in thymic epithelial cells: an evolutionary perspective for thymus atrophy.Clinical epigenetics · 2021Review
- Article
- Metabolic Regulation of Thymic Epithelial Cell Function.Frontiers in immunology · 2021Review
- Involvement of Gut Microbiota, Microbial Metabolites and Interaction with Polyphenol in Host Immunometabolism.Nutrients · 2020Review
- T cell Tolerance in Early Life.Frontiers in immunology · 2020Review
- Spaceflight/microgravity inhibits the proliferation of hematopoietic stem cells by decreasing Kit-Ras/cAMP-CREB pathway networks as evidenced by RNA-Seq assays.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Class II MHC antigen processing in immune tolerance and inflammation.Immunogenetics · 2019Review
- Thymic Epithelial Cells Contribute to Thymopoiesis and T Cell Development.Frontiers in immunology · 2019Review
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thymic epithelial cells (TECs) are critical for the establishment and maintenance of appropriate microenvironment for the positive and negative selection of thymocytes and the induction of central immune tolerance. Yet, little about the molecular regulatory network on TEC development and function is understood. Here, we demonstrate that MTOR (mechanistic target of rapamycin [serine/threonine kinase]) is essential for proper development and functional maturation of TECs. Pharmacological inhibition of MTOR activity by rapamycin (RPM) causes severe thymic atrophy and reduction of TECs. TEC-specific deletion of Mtor causes the severe reduction of mTECs, the blockage of thymocyte differentiation and output, the reduced generation of thymic regulatory T (Treg) cells and the impaired expression of tissue-restricted antigens (TRAs) including Fabp2, Ins1, Tff3 and Chrna1 molecules. Importantly, specific deletion of Mtor in TECs causes autoimmune diseases characterized by enhanced tissue immune cell infiltration and the presence of autoreactive antibodies. Mechanistically, Mtor deletion causes overdegradation of CTNNB1/Beta-Catenin due to excessive autophagy and the attenuation of WNT (wingless-type MMTV integration site family) signaling in TECs. Selective inhibition of autophagy significantly rescued the poor mTEC development caused by Mtor deficiency. Altogether, MTOR is essential for TEC development and maturation by regulating proliferation and WNT signaling activity through autophagy. The present study also implies that long-term usage of RPM might increase the risk of autoimmunity by impairing TEC maturation and function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.