PMID- 22815285 OWN - NLM STAT- MEDLINE DCOM- 20121019 LR - 20211021 IS - 1550-6606 (Electronic) IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 189 IP - 4 DP - 2012 Aug 15 TI - A critical role for Rictor in T lymphopoiesis. PG - 1850-7 LID - 10.4049/jimmunol.1201057 [doi] AB - Apart from a critical role for Notch and pre-TCR, the signaling pathway required for T lymphopoiesis is largely unknown. Given the potential link between Notch and mammalian target of rapamycin (mTOR) signaling in cancer cells, we used mice with conditional deletion of either Raptor or Rictor genes to determine potential contribution of the mTOR complex I and II in T lymphopoiesis. Our data demonstrated that targeted mutation of Rictor in the thymocytes drastically reduced the thymic cellularity, primarily by reducing proliferation of the immature thymocytes. Rictor deficiency caused a partial block of thymocyte development at the double-negative 3 stage. The effect of Rictor deficiency is selective for the T cell lineage, as the development of B cells, erythrocytes, and myeloid cells is largely unaffected. Analysis of bone marrow chimera generated from a mixture of wild-type and Rictor-deficient hematopoietic stem cells demonstrated that the function of Rictor is cell intrinsic. These data revealed a critical function of mTOR complex 2 in T lymphopoiesis. FAU - Tang, Fei AU - Tang F AD - Division of Immunotherapy, Department of Surgery, University of Michigan Medical School and Comprehensive Cancer Center, Ann Arbor, MI 48109, USA. FAU - Wu, Qi AU - Wu Q FAU - Ikenoue, Tsuneo AU - Ikenoue T FAU - Guan, Kun-Liang AU - Guan KL FAU - Liu, Yang AU - Liu Y FAU - Zheng, Pan AU - Zheng P LA - eng GR - R01 CA058033/CA/NCI NIH HHS/United States GR - R01 AI064350/AI/NIAID NIH HHS/United States GR - R01 AG036690/AG/NIA NIH HHS/United States GR - R01AG036690/AG/NIA NIH HHS/United States GR - AI64350/AI/NIAID NIH HHS/United States GR - RC1 GM091648/GM/NIGMS NIH HHS/United States GR - CA58033/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20120718 PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Carrier Proteins) RN - 0 (Rapamycin-Insensitive Companion of mTOR Protein) RN - 0 (Regulatory-Associated Protein of mTOR) RN - 0 (Rptor protein, mouse) RN - 0 (rictor protein, mouse) SB - IM MH - Adaptor Proteins, Signal Transducing MH - Animals MH - Carrier Proteins/*immunology/metabolism MH - Cell Differentiation/genetics/*immunology MH - Flow Cytometry MH - Lymphopoiesis/genetics/*immunology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Precursor Cells, T-Lymphoid/cytology/*immunology MH - Rapamycin-Insensitive Companion of mTOR Protein MH - Real-Time Polymerase Chain Reaction MH - Regulatory-Associated Protein of mTOR MH - T-Lymphocytes/cytology/*immunology PMC - PMC3412163 MID - NIHMS388117 EDAT- 2012/07/21 06:00 MHDA- 2012/10/20 06:00 PMCR- 2013/08/15 CRDT- 2012/07/21 06:00 PHST- 2012/07/21 06:00 [entrez] PHST- 2012/07/21 06:00 [pubmed] PHST- 2012/10/20 06:00 [medline] PHST- 2013/08/15 00:00 [pmc-release] AID - jimmunol.1201057 [pii] AID - 10.4049/jimmunol.1201057 [doi] PST - ppublish SO - J Immunol. 2012 Aug 15;189(4):1850-7. doi: 10.4049/jimmunol.1201057. Epub 2012 Jul 18.