AMP‐activated Protein kinase regulates FasL expression in Jurkat T lymphocytes via NF‐AT and AP‐1 dependent pathways

Abstract

T cell activation by T cell receptor (TCR) engagement or its pharmacological mimics induces FasL expression to maintain T cell homeostasis by apoptosis of activated T cells. AMP‐activated protein kinase (AMPK), an important regulator of energy homeostasis, is known to be activated during T cell activation. In this study, we examined the roles and signaling mechanisms of AMPK in T cell receptor‐induced FasL expression. AMPK is activated at the downstream of Ca2+/CaMKK during T cell receptor activation. Inhibition of AMPK by pharmacological agent or small interfering RNA suppressed FasL expression as well as secretion of FasL protein in T cells stimulated with PMA plus ionomycin (PMA/Io) or with monoclonal anti‐CD3 plus anti‐CD28 (CD3/CD28). Consistently, inhibition of AMPK blocked promoter activity of FasL in Jurkat T cells. We found that inhibition of AMPK reduced transcriptional activation NF‐AT and AP‐1 in Jurkat T cells. Furthermore, we found that inhibition of AMPK blocked phosphorylation and activation of PKC‐theta, a critical molecule in T cell activation and FasL expression. Taken together, our results show that AMPK regulates T cell receptor‐induced FasL expression through activation of NF‐AT and AP‐1 pathways in Jurkat T cells and imply that AMPK may play a role in activation‐induced cell death during T cell activation.This work was supported by grants from KOSEF and KRF of Korea Government.