The Interleukin-2-mTORc1 Kinase Axis Defines the Signaling, Differentiation, and Metabolism of T Helper 1 and Follicular B Helper T Cells.

Détails

ID Serval
serval:BIB_E99535EA33C0
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The Interleukin-2-mTORc1 Kinase Axis Defines the Signaling, Differentiation, and Metabolism of T Helper 1 and Follicular B Helper T Cells.
Périodique
Immunity
Auteur(s)
Ray J.P., Staron M.M., Shyer J.A., Ho P.C., Marshall H.D., Gray S.M., Laidlaw B.J., Araki K., Ahmed R., Kaech S.M., Craft J.
ISSN
1097-4180 (Electronic)
ISSN-L
1074-7613
Statut éditorial
Publié
Date de publication
20/10/2015
Peer-reviewed
Oui
Volume
43
Numéro
4
Pages
690-702
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
The differentiation of CD4(+) helper T cell subsets with diverse effector functions is accompanied by changes in metabolism required to meet their bioenergetic demands. We find that follicular B helper T (Tfh) cells exhibited less proliferation, glycolysis, and mitochondrial respiration, accompanied by reduced mTOR kinase activity compared to T helper 1 (Th1) cells in response to acute viral infection. IL-2-mediated activation of the Akt kinase and mTORc1 signaling was both necessary and sufficient to shift differentiation away from Tfh cells, instead promoting that of Th1 cells. These findings were not the result of generalized signaling attenuation in Tfh cells, because they retained the ability to flux calcium and activate NFAT-transcription-factor-dependent cytokine production. These data identify the interleukin-2 (IL-2)-mTORc1 axis as a critical orchestrator of the reciprocal balance between Tfh and Th1 cell fates and their respective metabolic activities after acute viral infection.
Mots-clé
Animals, Apoptosis, Calcium Signaling, Cell Cycle, Cell Division, Enzyme Activation, Glucose/metabolism, Glycolysis, Interleukin-2/physiology, Interleukin-2 Receptor alpha Subunit/physiology, Lymphocytic choriomeningitis virus/immunology, Mechanistic Target of Rapamycin Complex 1, Mice, Inbred C57BL, Multiprotein Complexes/physiology, NFATC Transcription Factors/physiology, Oxygen Consumption, Positive Regulatory Domain I-Binding Factor 1, Proto-Oncogene Proteins c-akt/physiology, Signal Transduction/physiology, Specific Pathogen-Free Organisms, T-Lymphocyte Subsets/cytology, T-Lymphocyte Subsets/immunology, T-Lymphocyte Subsets/metabolism, T-Lymphocytes, Helper-Inducer/cytology, T-Lymphocytes, Helper-Inducer/immunology, T-Lymphocytes, Helper-Inducer/metabolism, T-Lymphocytes, Helper-Inducer/virology, TOR Serine-Threonine Kinases/physiology, Th1 Cells/cytology, Th1 Cells/immunology, Th1 Cells/metabolism, Transcription Factors/biosynthesis, Transcription Factors/genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
05/04/2019 16:21
Dernière modification de la notice
20/08/2019 17:12
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