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- Title
PPARβ/δ-orchestrated metabolic reprogramming supports the formation and maintenance of memory CD8<sup>+</sup> T cells.
- Authors
Bevilacqua, Alessio; Franco, Fabien; Lu, Ya-Ting; Rahiman, Nabil; Kao, Kung-Chi; Chuang, Yu-Ming; Zhu, Yanan; Held, Werner; Xie, Xin; Gunsalus, Kristin C.; Xiao, Zhengtao; Chen, Shih-Yu; Ho, Ping-Chih
- Abstract
The formation of memory T cells is a fundamental feature of adaptative immunity, allowing the establishment of long-term protection against pathogens. Although emerging evidence suggests that metabolic reprogramming is crucial for memory T cell differentiation and survival, the underlying mechanisms that drive metabolic rewiring in memory T cells remain unclear. Here, we found that up-regulation of the nuclear receptor peroxisome proliferator–activated receptor β/δ (PPARβ/δ) instructs the metabolic reprogramming that occurs during the establishment of central memory CD8+ T cells. PPARβ/δ-regulated changes included suppression of aerobic glycolysis and enhancement of oxidative metabolism and fatty acid oxidation. Mechanistically, exposure to interleukin-15 and expression of T cell factor 1 facilitated activation of the PPARβ/δ pathway, counteracting apoptosis induced by antigen clearance and metabolic stress. Together, our findings indicate that PPARβ/δ is a master metabolic regulator orchestrating a metabolic switch that may be favorable for T cell longevity. Editor's summary: After initial antigen encounter, some T cells persist and differentiate into long-lived memory cells. This process is accompanied by metabolic reprogramming that supports survival and memory functions, but the key factors driving memory T cell metabolic adaptation remain unclear. Using mouse models of viral infection and melanoma, Bevilacqua et al. found that the nuclear receptor peroxisome proliferator–activated receptor β/δ (PPARβ/δ) supports the switch from aerobic glycolysis to oxidative metabolism during central memory CD8+ T cell formation. PPARβ/δ expression was required for memory T cell responses upon rechallenge, as well as the generation of TCF-1+ progenitor exhausted T cells during chronic antigen exposure. Together, these findings identify PPARβ/δ as a key regulator of metabolic reprogramming during memory T cell differentiation. —Claire Olingy
- Subjects
METABOLIC reprogramming; T cell differentiation; IMMUNOLOGIC memory; FATTY acid oxidation; T cells
- Publication
Science Immunology, 2024, Vol 9, Issue 98, p1
- ISSN
2470-9468
- Publication type
Article
- DOI
10.1126/sciimmunol.adn2717