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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Papadopoulou, G; Valakos, D; Polydouri, I; Moulara, A; Vatsellas, G; Angiari, S; Runtsch, MC; Foretz, M; Viollet, B; Cassotta, A; O'Neill, LAJ; Xanthou, G.
Adenosine 2A receptor-dependent activation of AMPK represses TH17 cell pathogenicity through epigenetic and metabolic reprogramming.
Sci Signal. 2025; 18(905):eadr3177
Doi: 10.1126/scisignal.adr3177
PubMed
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- Co-Autor*innen der Med Uni Graz
- Angiari Stefano
- Runtsch Marah
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- Abstract:
- Metabolic reprogramming controls protective and pathogenic T helper 17 (TH17) cell responses. When naïve T cells are differentiated into TH17 cells in vitro, the presence of the cytokine activin A promotes their maturation into a nonpathogenic state. Here, we found that nonpathogenic TH17 cells induced by activin A displayed reduced aerobic glycolysis and increased oxidative phosphorylation (OXPHOS). In response to activin A, signaling through the adenosine A2A receptor (A2AR) and AMP-activated protein kinase (AMPK) enhanced OXPHOS and reprogrammed pathogenic TH17 cells toward nonpathogenic states that did not induce central nervous system autoimmunity in a mouse model of multiple sclerosis. In pathogenic TH17 cells, the transcriptional coactivator p300/CBP-associated factor (PCAF) increased acetylation at histone 3 Lys9 (H3K9ac) of genes involved in aerobic glycolysis and TH17 pathogenic programs. In contrast, in nonpathogenic activin A-treated TH17 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 TH17 programs. Together, our findings uncover A2AR-AMPK signaling as a central metabolic checkpoint that suppresses TH17 cell pathogenicity.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals - administration & dosage
- Receptor, Adenosine A2A - metabolism, immunology, genetics
- Th17 Cells - immunology, metabolism, pathology
- AMP-Activated Protein Kinases - metabolism, genetics, immunology
- Mice - administration & dosage
- Epigenesis, Genetic - immunology
- Signal Transduction - immunology
- Histones - metabolism
- Oxidative Phosphorylation - administration & dosage
- Glycolysis - administration & dosage
- Mice, Inbred C57BL - administration & dosage
- p300-CBP Transcription Factors - metabolism, genetics, immunology
- Multiple Sclerosis - immunology, metabolism, pathology, genetics
- Encephalomyelitis, Autoimmune, Experimental - immunology, pathology, metabolism
- Cell Differentiation - administration & dosage
- Acetylation - administration & dosage
- Metabolic Reprogramming - administration & dosage