LKB1 and AMPK: central regulators of lymphocyte metabolism and function

Abstract

When T cells encounter foreign antigen and appropriate costimulatory signals from professional antigen-presenting cells (APCs), they initiate a coordinated program of rapid proliferation and differentiation, leading to the development of activated T cells with specific effector functions tailored toward pathogen clearance or control. One of the fundamental programs that underpin T-cell proliferation and function is the regulation of cellular metabolism. Recent efforts to identify the signal transduction pathways that regulate T-cell metabolism have led to the identification of liver kinase B1 (LKB1) and AMP-activated protein kinase (AMPK) as key regulators of T-cell metabolism. LKB1 and AMPK are part of an evolutionarily conserved signal transduction pathway that monitors cellular energy status. AMPK senses bioenergetic fluctuations in cells and works in concert with LKB1 to maintain cellular energy homeostasis by promoting catabolic pathways of ATP production and limiting processes that consume ATP. Recent data indicate that LKB1 and AMPK can influence diverse aspects of T-cell biology beyond metabolism, including T-cell development, peripheral T-cell homeostasis, and T-cell effector function. In this review, we focus on the regulation of lymphocyte metabolism by this energy-sensing pathway and discuss its influence on T-cell function.