Work

Metabolic Drivers of T Cell Migration: Distinct Roles of CCL21 and IL-7 in ATP Production and Motility 3199

Year: 2025

Type: article

Abstract: Description T cell migration through peripheral tissues is essential for immune surveillance, while their movement through lymph nodes is crucial for interacting with dendritic cells, leading to activation. This movement is triggered by CCL21 signaling through chemokine receptor, CCR7, and requires a constant supply of energy to meet motility demands. Even so, the intersection between signaling through CCR7 and metabolic processes that drive this movement remain poorly understood. Alternatively, it is well established that signaling through IL-7R will induce T cells to utilize glycolysis to promote T cell survival. However, it remains unclear if signaling through IL-7R also affects T cell movement. In this study, we utilize Seahorse analysis to investigate the metabolic pathways that drive naïve T cell migration in response to CCL21 and IL-7. We observed CCL21 decreases respiratory capacity, yet has no effect on glycolysis, while IL-7 promotes glycolysis and has no effect on cellular respiration. Using inhibitors of key metabolic pathways, we demonstrate that mitochondrial respiration is required for CCL21 and IL-7 induced migration of T cells, while glycolysis appears to be dispensable for migration. Our results offer insights into the interplay between metabolism and motility, indicating distinct mechanisms of ATP production that facilitate T cell movement. Funding Sources KAM is supported by the Academic Science Education and Research Training (ASERT) Program (K12 GM088021); JRB was supported by NIH 5 T32 AI007538 and JLC is supported by KL2 (KL2TR001448). This work was supported by funding from the following: NIH 1R01AI097202 (JLC), the Spatiotemporal Modeling Center (P50 GM085273), pilot funds from NM-INSPIRES 1P30ES032755 (JLC). Topic Categories Cellular Adhesion, Migration, and Inflammation (CAM)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.1025