PPARβ/δ-orchestrated metabolic reprogramming supports the formation and maintenance of memory CD8 + T cells.

Autor:	Bevilacqua A; Department of Oncology, University of Lausanne, Lausanne, Switzerland.; Ludwig Institute for Cancer Research, University of Lausanne, Epalinges, Switzerland., Franco F; Department of Oncology, University of Lausanne, Lausanne, Switzerland.; Ludwig Institute for Cancer Research, University of Lausanne, Epalinges, Switzerland., Lu YT; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Rahiman N; Center for Genomics and System Biology (CSGB), New York University Abu Dhabi, Abu Dhabi, United Arab Emirates., Kao KC; Department of Oncology, University of Lausanne, Lausanne, Switzerland.; Ludwig Institute for Cancer Research, University of Lausanne, Epalinges, Switzerland., Chuang YM; Department of Oncology, University of Lausanne, Lausanne, Switzerland.; Ludwig Institute for Cancer Research, University of Lausanne, Epalinges, Switzerland., Zhu Y; School of Basic Medical Sciences, Xi'an Jiao Tong University Health Science Center, Xi'an, Shaanxi, China., Held W; Department of Oncology, University of Lausanne, Lausanne, Switzerland., Xie X; Center for Genomics and System Biology (CSGB), New York University Abu Dhabi, Abu Dhabi, United Arab Emirates.; School of Life and Environmental Sciences, Shaoxing University, Shaoxing City, Zhejiang, China., Gunsalus KC; Center for Genomics and System Biology (CSGB), New York University Abu Dhabi, Abu Dhabi, United Arab Emirates.; Center for Genomics and Systems Biology, New York University, New York, NY, USA., Xiao Z; School of Basic Medical Sciences, Xi'an Jiao Tong University Health Science Center, Xi'an, Shaanxi, China., Chen SY; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Ho PC; Department of Oncology, University of Lausanne, Lausanne, Switzerland.; Ludwig Institute for Cancer Research, University of Lausanne, Epalinges, Switzerland.
Jazyk:	angličtina
Zdroj:	Science immunology [Sci Immunol] 2024 Aug 23; Vol. 9 (98), pp. eadn2717. Date of Electronic Publication: 2024 Aug 23.
DOI:	10.1126/sciimmunol.adn2717
Abstrakt:	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.
Databáze:	MEDLINE
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