| Title: |
Adenosine 2A receptor–dependent activation of AMPK represses T H 17 cell pathogenicity through epigenetic and metabolic reprogramming |
| Authors: |
Papadopoulou, Gina; Valakos, Dimitrios; Polydouri, Ioanna; Moulara, Afroditi; Vatsellas, Giannis; Angiari, Stefano; Runtsch, Marah; Foretz, Marc; Viollet, Benoit; O’neill, Luke; Cassotta, Antonino; Xanthou, Georgina |
| Contributors: |
Biomedical Research Foundation of the Academy of Athens (BRFAA); Aristotle University of Thessaloniki; Medical University of Graz = Medizinische Universität Graz; Trinity College Dublin; Institut Cochin (IC UM3 (UMR 8104 / U1016)); Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité) |
| Source: |
ISSN: 1937-9145. |
| Publisher Information: |
CCSD; American Association for the Advancement of Science (AAAS) |
| Publication Year: |
2025 |
| Subject Terms: |
[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity; [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry; Molecular Biology/Biochemistry [q-bio.BM]; [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]; [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology |
| Description: |
International audience ; Metabolic reprogramming controls protective and pathogenic T helper 17 (T H 17) cell responses. When naïve T cells are differentiated into T H 17 cells in vitro, the presence of the cytokine activin A promotes their maturation into a nonpathogenic state. Here, we found that nonpathogenic T H 17 cells induced by activin A displayed reduced aerobic glycolysis and increased oxidative phosphorylation (OXPHOS). In response to activin A, signaling through the adenosine A 2A receptor (A 2A R) and AMP-activated protein kinase (AMPK) enhanced OXPHOS and reprogrammed pathogenic T H 17 cells toward nonpathogenic states that did not induce central nervous system autoimmunity in a mouse model of multiple sclerosis. In pathogenic T H 17 cells, the transcriptional coactivator p300/CBP-associated factor (PCAF) increased acetylation at histone 3 Lys 9 (H3K9ac) of genes involved in aerobic glycolysis and T H 17 pathogenic programs. In contrast, in nonpathogenic activin A–treated T H 17 cells, AMPK signaling suppressed PCAF-mediated H3K9ac modification of genes involved in aerobic metabolism and enhanced H3K9ac modification of genes involved in OXPHOS and nonpathogenic T H 17 programs. Together, our findings uncover AA 2A R-AMPK signaling as a central metabolic checkpoint that suppresses T H 17 cell pathogenicity. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1126/scisignal.adr3177 |
| Availability: |
https://hal.science/hal-05398095; https://hal.science/hal-05398095v1/document; https://hal.science/hal-05398095v1/file/adr3177_ArticleContent_v2.pdf; https://doi.org/10.1126/scisignal.adr3177 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.3A4EACE0 |
| Database: |
BASE |