The Interleukin-2-mTORc1 Axis Defines the Reciprocal Signaling, Differentiation, and Metabolism of T Helper 1 and Follicular B Helper T Cells
| Autor: | Ray, John P., Staron, Matthew M., Shyer, Justin A., Ho, Ping-Chih, Marshall, Heather D., Gray, Simon M., Laidlaw, Brian J., Araki, Koichi, Ahmed, Rafi, Kaech, Susan M., Craft, Joe |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Apoptosis
Mechanistic Target of Rapamycin Complex 1 Article Oxygen Consumption T-Lymphocyte Subsets Animals Lymphocytic choriomeningitis virus Calcium Signaling NFATC Transcription Factors TOR Serine-Threonine Kinases Cell Cycle Interleukin-2 Receptor alpha Subunit T-Lymphocytes Helper-Inducer Th1 Cells Specific Pathogen-Free Organisms Enzyme Activation Mice Inbred C57BL Glucose Multiprotein Complexes Interleukin-2 Positive Regulatory Domain I-Binding Factor 1 Glycolysis Proto-Oncogene Proteins c-akt Cell Division Signal Transduction Transcription Factors |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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