Phosphoinositide 3-kinase (PI3K) and nutrient sensing mTOR (mammalian target of rapamycin) pathways control T lymphocyte trafficking

PI3K and mTOR are evolutionarily conserved regulators of cell metabolism. Here we show PI3K and mTOR determine the repertoire of adhesion and chemokine receptors expressed by T lymphocytes. Key lymph node homing receptors, CD62L (L-selectin) and CCR7, are highly expressed on naive T lymphocytes but downregulated following immune activation. CD62L downregulation occurs via ectodomain proteolysis and suppression of gene transcription. PI3K p110δ controls CD62L proteolysis via mitogen-activated protein (MAP) kinases whereas PI3K p110δ control of CD62L transcription is mediated by the nutrient sensor mTOR via regulation of the transcription factor KLF2. PI3K-mTOR nutrient sensing pathways also determined expression of the chemokine receptor CCR7 and regulate lymphocyte trafficking in vivo . Hence, lymphocytes utilize PI3K and mTOR to match metabolism and trafficking.