IL-7R and CCR7 Regulate Distinct Metabolic Pathways in Naïve T Cells to Promote T Cell Motility

Naïve T cells movement through tissues, including through lymph nodes, requires ongoing energy supply for rapid motility promoting T cell scanning of dendritic cells and T cell activation. Rapid movement is facilitated by signaling through chemokine receptor CCR7, but how signaling to motility relates to T cell metabolism is not well understood. Conversely, whether signals including IL-7R which are known to regulate naïve T cell metabolism might impact motility is not known. We analyze how CCR7 and IL-7R regulate T cell motility and metabolism. Using Seahorse analysis, we find that CCL21 signaling to CCR7 decreases oxidative phosphorylation, but has no effect on glycolysis. In contrast, IL-7 promotes glycolysis but shows no effect on respiration. We demonstrate a previously unidentified role for IL-7/IL-7R in promotion of T cell motility in lymph nodes by imaging T cell movement in lymph nodes after inhibition of IL-7R and IL-7. Downstream of IL-7R, JAK3 and STAT5, but not mTOR, mediates rapid motility. Our results shed new light on how metabolism intersects with motility to promote more efficient T cell movement within lymph nodes to promote potential for DC scanning and interaction, potentially through differential means of ATP production.