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

// Enyu Rao 1 , Yuwen Zhang 1 , Qiang Li 2 , Jiaqing Hao 1 , Nejat K. Egilmez 1 , Jill Suttles 1 and Bing Li 1 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, Ca 2+ -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”.