{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T16:43:15Z","timestamp":1784824995225,"version":"3.55.0"},"reference-count":46,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"905","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Signal."],"published-print":{"date-parts":[[2025,9,23]]},"abstract":"<jats:p>\n            Metabolic reprogramming controls protective and pathogenic T helper 17 (T\n            <jats:sub>H<\/jats:sub>\n            17) cell responses. When na\u00efve T cells are differentiated into T\n            <jats:sub>H<\/jats:sub>\n            17 cells in vitro, the presence of the cytokine activin A promotes their maturation into a nonpathogenic state. Here, we found that nonpathogenic T\n            <jats:sub>H<\/jats:sub>\n            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\n            <jats:sub>2A<\/jats:sub>\n            receptor (A\n            <jats:sub>2A<\/jats:sub>\n            R) and AMP-activated protein kinase (AMPK) enhanced OXPHOS and reprogrammed pathogenic T\n            <jats:sub>H<\/jats:sub>\n            17 cells toward nonpathogenic states that did not induce central nervous system autoimmunity in a mouse model of multiple sclerosis. In pathogenic T\n            <jats:sub>H<\/jats:sub>\n            17 cells, the transcriptional coactivator p300\/CBP-associated factor (PCAF) increased acetylation at histone 3 Lys\n            <jats:sup>9<\/jats:sup>\n            (H3K9ac) of genes involved in aerobic glycolysis and T\n            <jats:sub>H<\/jats:sub>\n            17 pathogenic programs. In contrast, in nonpathogenic activin A\u2013treated T\n            <jats:sub>H<\/jats:sub>\n            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\n            <jats:sub>H<\/jats:sub>\n            17 programs. Together, our findings uncover A\n            <jats:sub>2A<\/jats:sub>\n            R-AMPK signaling as a central metabolic checkpoint that suppresses T\n            <jats:sub>H<\/jats:sub>\n            17 cell pathogenicity.\n          <\/jats:p>","DOI":"10.1126\/scisignal.adr3177","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T17:58:23Z","timestamp":1758650303000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Adenosine 2A receptor\u2013dependent activation of AMPK represses T\n            <sub>H<\/sub>\n            17 cell pathogenicity through epigenetic and metabolic reprogramming"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3022-4350","authenticated-orcid":true,"given":"Gina","family":"Papadopoulou","sequence":"first","affiliation":[{"name":"Cellular Immunology Laboratory, Center of Basic Research, Biomedical Research Foundation of the Academy of Athens, 115 27 Athens, Greece."},{"name":"Department of Genetics, Development, and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios","family":"Valakos","sequence":"additional","affiliation":[{"name":"Molecular Biology Laboratory, Center of Basic Research, Biomedical Research Foundation of the Academy of Athens, 115 27 Athens, Greece."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioanna","family":"Polydouri","sequence":"additional","affiliation":[{"name":"Molecular Biology Laboratory, Center of Basic Research, Biomedical Research Foundation of the Academy of Athens, 115 27 Athens, Greece."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afroditi","family":"Moulara","sequence":"additional","affiliation":[{"name":"Cellular Immunology Laboratory, Center of Basic Research, Biomedical Research Foundation of the Academy of Athens, 115 27 Athens, Greece."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1631-1060","authenticated-orcid":true,"given":"Giannis","family":"Vatsellas","sequence":"additional","affiliation":[{"name":"Molecular Biology Laboratory, Center of Basic Research, Biomedical Research Foundation of the Academy of Athens, 115 27 Athens, Greece."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Angiari","sequence":"additional","affiliation":[{"name":"Division of Immunology, Otto Loewi Research Center, Medical University of Graz, A-8010 Graz, Austria."},{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, D02 R590 Dublin, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9059-9269","authenticated-orcid":true,"given":"Marah C.","family":"Runtsch","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, D02 R590 Dublin, Ireland."},{"name":"Division of Oncology, Otto Loewi Research Center, Medical University of Graz, A-8010 Graz, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7017-9032","authenticated-orcid":true,"given":"Marc","family":"Foretz","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS, Inserm, Institut Cochin, 75014 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0121-0224","authenticated-orcid":true,"given":"Benoit","family":"Viollet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS, Inserm, Institut Cochin, 75014 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8674-4294","authenticated-orcid":true,"given":"Antonino","family":"Cassotta","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine, Universit\u00e0 della Svizzera italiana, 6500 Bellinzona, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4333-2748","authenticated-orcid":true,"given":"Luke A. J.","family":"O\u2019Neill","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, D02 R590 Dublin, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7944-2343","authenticated-orcid":true,"given":"Georgina","family":"Xanthou","sequence":"additional","affiliation":[{"name":"Cellular Immunology Laboratory, Center of Basic Research, Biomedical Research Foundation of the Academy of Athens, 115 27 Athens, Greece."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-022-01387-9"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04754"},{"key":"e_1_3_2_4_2","first-page":"991","article-title":"Induction and molecular signature of pathogenic TH17 cells","volume":"13","author":"Lee Y.","year":"2012","unstructured":"Y. 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