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

Markus M. Xie, Tohti Amet, Hong Liu, Andy Yu, Alexander Dent

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The 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.

Original languageEnglish (US)
Pages (from-to)67-75
Number of pages9
JournalMolecular Immunology
Volume81
DOIs
StatePublished - Jan 1 2017

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Adenylate Kinase
T-Lymphocytes
Cell Differentiation
Interleukin-2
Glucose
Deoxyglucose
Glycolysis
Up-Regulation
AMP-Activated Protein Kinases
Helper-Inducer T-Lymphocytes
Antibody Formation
Transcription Factors
Pharmaceutical Preparations

Keywords

  • AMPK
  • Bcl6
  • Metabolism
  • T follicular helper cells

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

Cite this

AMP kinase promotes Bcl6 expression in both mouse and human T cells. / Xie, Markus M.; Amet, Tohti; Liu, Hong; Yu, Andy; Dent, Alexander.

In: Molecular Immunology, Vol. 81, 01.01.2017, p. 67-75.

Research output: Contribution to journalArticle

Xie, Markus M. ; Amet, Tohti ; Liu, Hong ; Yu, Andy ; Dent, Alexander. / AMP kinase promotes Bcl6 expression in both mouse and human T cells. In: Molecular Immunology. 2017 ; Vol. 81. pp. 67-75.
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