ORIGINAL RESEARCH article
Front. Immunol.
Sec. T Cell Biology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1571221
Effector Tc17 cells resist shift from OXPHOS to aerobic glycolysis
Provisionally accepted
- 1Department of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana–Champaign, Urbana, Illinois, United States
- 2Cancer Center at Illinois, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States
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IL-17A-expressing lymphocytes, including Tc17 cells, are instrumental in immunity, immunopathology, and autoimmunity. We have previously shown that experimental attenuated live fungal vaccine-induced Tc17 cells are stable, long-lived without plasticity, and necessary to mediate sterilizing immunity during CD4+ T cell deficiency, which poses higher susceptibility to fungal infections. Cell metabolism is integral for T cell homeostasis but the metabolic adaptations of Tc17 cells are poorly defined. In this study, we hypothesized that effector Tc17 cells adopt high energy-yielding metabolic pathways to form stable, long-lived memory cells in vivo. Using a mouse model of attenuated fungal vaccination, we found that effector Tc17 cells were metabolically highly active with higher proliferation and protein synthesis than IFN+ CD8+ T (Tc1) cells. Glucose was necessary for effector Tc17 cell expansion but with less dependency during the late expansion despite the active metabolism. Contrary to established dogma, we found that the effector Tc17 cells preferentially channeled the glucose to OXPHOS than glycolysis, which was correlated with higher mitochondrial mass and membrane potential. Inhibition of OXPHOS shrunk the Tc17 responses while sparing Tc1 cell responses. Tc17 cells actively relied on OXPHOS throughout the expansion period, resisting adaptation to aerobic glycolysis. Our data showed that the effector Tc17 cells predominantly utilize glucose for metabolism through OXPHOS rather than aerobic glycolysis. Our study has implications in vaccine design to enhance the efficacy and immunotherapeutics to modulate the immunity and autoimmunity.
Keywords: CD8 + T cell, Tc17 cell, Glycolysis, OxPhos, T cell activation, Antifungal, vaccine responses
Received: 05 Feb 2025; Accepted: 28 Apr 2025.
Copyright: © 2025 John, Mudalagiriyappa, Chandrashekar and Nanjappa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Som G. Nanjappa, Department of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana–Champaign, Urbana, 61802, Illinois, United States
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