Abstract
| Original language | English |
|---|---|
| Article number | e106710 |
| Number of pages | 7 |
| Journal | PLoS ONE |
| Volume | 9 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 2 Sep 2014 |
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Adenosine-mono-phosphate-activated protein kinase-independent effects of metformin in T cells. / Zarrouk, Marouan; Finlay, David K.; Foretz, Marc; Viollet, Benoit; Cantrell, Doreen A. (Lead / Corresponding author).
In: PLoS ONE, Vol. 9, No. 9, e106710, 02.09.2014.Research output: Contribution to journal › Article
TY - JOUR
T1 - Adenosine-mono-phosphate-activated protein kinase-independent effects of metformin in T cells
AU - Zarrouk, Marouan
AU - Finlay, David K.
AU - Foretz, Marc
AU - Viollet, Benoit
AU - Cantrell, Doreen A.
PY - 2014/9/2
Y1 - 2014/9/2
N2 - The anti-diabetic drug metformin regulates T-cell responses to immune activation and is proposed to function by regulating the energy-stress-sensing adenosine-monophosphate-activated protein kinase (AMPK). However, the molecular details of how metformin controls T cell immune responses have not been studied nor is there any direct evidence that metformin acts on T cells via AMPK. Here, we report that metformin regulates cell growth and proliferation of antigen-activated T cells by modulating the metabolic reprogramming that is required for effector T cell differentiation. Metformin thus inhibits the mammalian target of rapamycin complex I signalling pathway and prevents the expression of the transcription factors c-Myc and hypoxia-inducible factor 1 alpha. However, the inhibitory effects of metformin on T cells did not depend on the expression of AMPK in T cells. Accordingly, experiments with metformin inform about the importance of metabolic reprogramming for T cell immune responses but do not inform about the importance of AMPK.
AB - The anti-diabetic drug metformin regulates T-cell responses to immune activation and is proposed to function by regulating the energy-stress-sensing adenosine-monophosphate-activated protein kinase (AMPK). However, the molecular details of how metformin controls T cell immune responses have not been studied nor is there any direct evidence that metformin acts on T cells via AMPK. Here, we report that metformin regulates cell growth and proliferation of antigen-activated T cells by modulating the metabolic reprogramming that is required for effector T cell differentiation. Metformin thus inhibits the mammalian target of rapamycin complex I signalling pathway and prevents the expression of the transcription factors c-Myc and hypoxia-inducible factor 1 alpha. However, the inhibitory effects of metformin on T cells did not depend on the expression of AMPK in T cells. Accordingly, experiments with metformin inform about the importance of metabolic reprogramming for T cell immune responses but do not inform about the importance of AMPK.
U2 - 10.1371/journal.pone.0106710
DO - 10.1371/journal.pone.0106710
M3 - Article
C2 - 25181053
VL - 9
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 9
M1 - e106710
ER -