Oncotarget

Research Papers: Immunology:

AMPK-dependent and independent effects of AICAR and compound C on T-cell responses

Enyu Rao, Yuwen Zhang, Qiang Li, Jiaqing Hao, Nejat K. Egilmez, Jill Suttles and Bing Li _

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Oncotarget. 2016; 7:33783-33795. https://doi.org/10.18632/oncotarget.9277

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Abstract

Enyu Rao1, Yuwen Zhang1, Qiang Li2, Jiaqing Hao1, Nejat K. Egilmez1, Jill Suttles1 and Bing Li1

1 Department of Microbiology and Immunology, University of Louisville, Louisville, KY, USA

2 Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong, University, Jinan, Shandong, China

Correspondence to:

Bing Li, email:

Keywords: AMPK, T cell responses, Immunology and Microbiology Section, Immune response, Immunity

Received: March 16, 2016 Accepted: April 27, 2016 Published: May 10, 2016

Abstract

As a master metabolic sensor, AMP-activated protein kinase (AMPK) is involved in different fundamental cellular processes. Regulation of AMPK activity either by agonists (e.g., AICAR) or by antagonists (e.g., Compound C) has been widely employed to study the physiological functions of AMPK. However, mounting evidence indicates AMPK-independent effects for these chemicals and how they regulate immune cell functions remains largely unknown. Herein, using T cells from AMPK conditional knockout mice and their wild type littermates, we demonstrate that AICAR and Compound C can, indeed, activate or inhibit AMPK activity in T cells, respectively. Specifically, AICAR inhibits, but Compound C promotes, Ca2+-induced T cell death in an AMPK-dependent manner. In contrast, our data also demonstrate that AICAR and Compound C inhibit T cell activation and cytokine production in an AMPK-independent manner. Moreover, we find that the AMPK-independent activity of AICAR and Compound Cis mediated via the mTOR signaling pathway in activated T cells. Our results not only reveal the critical role of AMPK in regulating T cell survival and function, but also demonstrate AMPK-dependent and independent rolesof AICAR/Compound C in regulating T cell responses, thus suggesting a context-dependent effect of these “AMPK regulators”.


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