AMP kinase promotes Bcl6 expression in both mouse and human T cells

dc.contributor.authorXie, Markus M.
dc.contributor.authorAmet, Tohti
dc.contributor.authorLiu, Hong
dc.contributor.authorYu, Qigui
dc.contributor.authorDent, Alexander L.
dc.contributor.departmentDepartment of Microbiology and Immunology, School of Medicineen_US
dc.date.accessioned2017-09-07T18:45:10Z
dc.date.available2017-09-07T18:45:10Z
dc.date.issued2017-01
dc.description.abstractThe transcription factor Bcl6 is a master regulator of follicular helper T (TFH) cells, and understanding the signaling pathway that induces Bcl6 and TFH cell differentiation is therefore critical. IL-2 produced during T cell activation inhibits Bcl6 expression but how TFH cells evade IL-2 inhibition is not completely understood. Here we show that Bcl6 is highly up-regulated in activated CD4 T cells following glucose deprivation (GD), and this pathway is insensitive to inhibition by IL-2. Similar to GD, the glucose analog 2-deoxyglucose (2DG) inhibits glycolysis, and 2DG induced Bcl6 expression in activated CD4 T cells. The metabolic sensor AMP kinase (AMPK) is activated when glycolysis is decreased, and the induction of Bcl6 by GD was inhibited by the AMPK antagonist compound C. Additionally, activation of AMPK by the drug AICAR caused Bcl6 up-regulation in activated CD4 T cells. When mice were immunized with KLH using AICAR as an adjuvant, there was a strong TFH–dependent enhancement of KLH-specific antibody (Ab) responses, and higher Bcl6 expression in TFH cells in vivo. Activation of AMPK strongly induced BCL6 and the up-regulation of TFH cell marker expression by human CD4 T cells. Our data reveal a major new pathway for TFH cell differentiation, conserved by both mouse and human T cells. Mature TFH cells are reported to have a lower metabolic state compared to TH1 cells. Our data indicates that decreased metabolism may be deterministic for TFH cell differentiation, and not simply a result of TFH cell differentiation.en_US
dc.eprint.versionAuthor's manuscripten_US
dc.identifier.citationXie, M. M., Amet, T., Liu, H., Yu, Q., & Dent, A. L. (2016). AMP kinase promotes Bcl6 expression in both mouse and human T cells. Molecular immunology, 81, 67. https://doi.org/10.1016/j.molimm.2016.11.020en_US
dc.identifier.urihttps://hdl.handle.net/1805/14050
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.isversionof10.1016/j.molimm.2016.11.020en_US
dc.relation.journalMolecular Immunologyen_US
dc.rightsPublisher Policyen_US
dc.sourceAuthoren_US
dc.subjectT follicular helper cellsen_US
dc.subjectBcl6en_US
dc.subjectmetabolismen_US
dc.titleAMP kinase promotes Bcl6 expression in both mouse and human T cellsen_US
dc.typeArticleen_US
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