Interleukin-7R and chemokine receptor type 7 differentially regulate metabolism in CD4+ and CD8+ T cells
Year: 2026
Type: article
Abstract: Naïve T cells are highly metabolically active, maintaining homeostatic function as well as continuously moving and surveying lymph nodes for dendritic cells (DCs) presenting cognate antigen. T-cell metabolism is thought to change throughout development: Naïve T cells have been found to predominantly utilize catabolism for naïve T-cell homeostasis while T-cell activation leads effector T cells to become glycolytic. There is still relatively less known about how individual and combinations of molecular signals drive specific metabolic programs in naïve T cells. Naïve T cells primarily depend on IL-7 signaling to IL-7R for homeostasis and are driven by the chemokine receptor CCR7 responding to CCL21 for rapid motility in lymph nodes, leading to T-cell surveillance. We identify specific roles for IL-7R and CCR7 in driving differential metabolic programs in naïve CD8+ and CD4+ T cells. We find that while IL-7 treatment increases glycolysis in both naïve CD4+ and CD8+ T cells, CCL21 treatment does not affect glycolysis. Instead, CCR7 signaling decreases respiratory capacity and mitochondrial intensity and area. While IL-7 treatment does not impact overall oxidative phosphorylation, IL-7 also alters mitochondrial dynamics. Interestingly, a combination of IL-7R and CCR7 signaling using IL-7 with CCL21 differentially affects CD4+ versus CD8+ T-cell metabolism. Our results demonstrate that multiple molecular signals can differentially regulate naïve CD4+ and CD8+ T-cell metabolism, leading to changes in both glycolysis and oxidative phosphorylation in naïve T cells.
Source: ImmunoHorizons
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,700
Awards: University of New Mexico (UNM) Center for Brain Recovery and Repair, Center for Spatiotemporal Modeling of Cell Signaling, Institutional Career Development Core, KL2 Scholars Program, The role of PKCtheta in T cell and T-ALL migration, Academic Science Education and Research Training, University of New Mexico Cancer Center Support Grant, New Mexico Integrative Science Program Incorporating Research in Environmental Sciences (NM-INSPIRES), Autophagy, Inflammation and Metabolism (AIM) in Disease Center - Phase 2., UNM Metals Exposure and Toxicity Assessment on tribal Lands in the Southwest (METALS) Superfund Research Program
OpenAlex ID: W7118797115