Academic Journal
The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment.
| Τίτλος: | The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment. |
|---|---|
| Συγγραφείς: | Delgoffe GM; Sidney-Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA., Kole TP, Zheng Y, Zarek PE, Matthews KL, Xiao B, Worley PF, Kozma SC, Powell JD |
| Πηγή: | Immunity [Immunity] 2009 Jun 19; Vol. 30 (6), pp. 832-44. |
| Τύπος έκδοσης: | Journal Article; Research Support, N.I.H., Extramural |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Cell Press Country of Publication: United States NLM ID: 9432918 Publication Model: Print Cited Medium: Internet ISSN: 1097-4180 (Electronic) Linking ISSN: 10747613 NLM ISO Abbreviation: Immunity Subsets: MEDLINE |
| Imprint Name(s): | Publication: Cambridge, MA : Cell Press Original Publication: Cambridge, Mass. : Cell Press, c1994- |
| Ιατρικοί όροι (MeSH): | Carrier Proteins/*metabolism , Cell Differentiation/*immunology , Phosphotransferases (Alcohol Group Acceptor)/*metabolism , T-Lymphocytes, Helper-Inducer/*immunology , T-Lymphocytes, Regulatory/*immunology , Trans-Activators/*immunology , Transcription Factors/*immunology, Carrier Proteins/genetics ; Carrier Proteins/immunology ; Interleukin-2/biosynthesis ; Interleukin-2/immunology ; Phosphotransferases (Alcohol Group Acceptor)/genetics ; Phosphotransferases (Alcohol Group Acceptor)/immunology ; Receptors, Antigen, T-Cell/immunology ; Receptors, Antigen, T-Cell/metabolism ; STAT Transcription Factors/immunology ; STAT Transcription Factors/metabolism ; Signal Transduction/immunology ; T-Lymphocytes, Helper-Inducer/enzymology ; T-Lymphocytes, Regulatory/enzymology ; Trans-Activators/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transforming Growth Factor beta/immunology ; Transforming Growth Factor beta/metabolism ; Animals ; Mice ; Mice, Knockout ; TOR Serine-Threonine Kinases |
| Περίληψη: | Effector T cell differentiation requires the simultaneous integration of multiple, and sometimes opposing, cytokine signals. We demonstrated mTOR's role in dictating the outcome of T cell fate. mTOR-deficient T cells displayed normal activation and IL-2 production upon initial stimulation. However, such cells failed to differentiate into T helper 1 (Th1), Th2, or Th17 effector cells. The inability to differentiate was associated with decreased STAT transcription factor activation and failure to upregulate lineage-specific transcription factors. Under normally activating conditions, T cells lacking mTOR differentiated into Foxp3(+) regulatory T cells. This was associated with hyperactive Smad3 activation in the absence of exogenous TGF-beta. Surprisingly, T cells selectively deficient in TORC1 do not divert to a regulatory T cell pathway, implicating both TORC1 and TORC2 in preventing the generation of regulatory T cells. Overall, our studies suggest that mTOR kinase signaling regulates decisions between effector and regulatory T cell lineage commitment. |
| Σχόλια: | Comment in: Immunity. 2009 Jun 19;30(6):759-61. doi: 10.1016/j.immuni.2009.06.002.. (PMID: 19538925) |
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| Grant Information: | R01CA14227 United States CA NCI NIH HHS; R01 CA098109 United States CA NCI NIH HHS; R01 AI077610 United States AI NIAID NIH HHS; R01CA098109 United States CA NCI NIH HHS; R01 CA114227 United States CA NCI NIH HHS |
| Substance Nomenclature: | 0 (Carrier Proteins) 0 (Crtc1 protein, mouse) 0 (Crtc2 protein, mouse) 0 (Interleukin-2) 0 (Receptors, Antigen, T-Cell) 0 (STAT Transcription Factors) 0 (Trans-Activators) 0 (Transcription Factors) 0 (Transforming Growth Factor beta) EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor)) EC 2.7.1.1 (mTOR protein, mouse) EC 2.7.11.1 (TOR Serine-Threonine Kinases) |
| Entry Date(s): | Date Created: 20090623 Date Completed: 20090717 Latest Revision: 20250529 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC2768135 |
| DOI: | 10.1016/j.immuni.2009.04.014 |
| PMID: | 19538929 |
| Βάση Δεδομένων: | MEDLINE |
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