The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment.

Λεπτομέρειες βιβλιογραφικής εγγραφής
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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Περιγραφή
ISSN:	1097-4180
DOI:	10.1016/j.immuni.2009.04.014