{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T18:36:54Z","timestamp":1788201414255,"version":"build-2803163510"},"reference-count":44,"publisher":"American Society for Clinical Investigation","issue":"17","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":42,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondazione Cariplo, University of Milan, Italian Ministry of University and Research","award":["2019-1560,PSR2022_DIP_022_AZIONE_A_FBONA,2022NBKCWP"],"award-info":[{"award-number":["2019-1560,PSR2022_DIP_022_AZIONE_A_FBONA,2022NBKCWP"]}]},{"name":"Italian Ministry of University and Research (PRIN), Italian Ministry of Health (Ricerca Finalizzata); European Commission","award":["2017 K55HLC,RF-2019-12370896,PNRR-MAD-2022-12375913,EUROPEAID\/173691\/DD\/ACT\/XK Nanokos"],"award-info":[{"award-number":["2017 K55HLC,RF-2019-12370896,PNRR-MAD-2022-12375913,EUROPEAID\/173691\/DD\/ACT\/XK Nanokos"]}]},{"name":"Fondazione Italiana Sclerosi Multipla (FISM), Italian Ministry of Health, Next Generation EU","award":["2022-PR-Single\/013,M6\/C2_CALL 2022 cod. PNRR-MAD-2022-12376126,NextGenerationEU\u2013 (P2022T4PKT)"],"award-info":[{"award-number":["2022-PR-Single\/013,M6\/C2_CALL 2022 cod. PNRR-MAD-2022-12376126,NextGenerationEU\u2013 (P2022T4PKT)"]}]},{"name":"Italian National Recovery and Resilience Plan (PNRR), Italian Ministry of Health, MUR\/PNRR Extended Partnership","award":["PNRR-MCNT2-2023-12378040,M6\/C2_CALL 2023,PNRR-MCNT2- 2023- 12378040,PE00000007,MNESYS no. PE00000006"],"award-info":[{"award-number":["PNRR-MCNT2-2023-12378040,M6\/C2_CALL 2023,PNRR-MCNT2- 2023- 12378040,PE00000007,MNESYS no. PE00000006"]}]},{"name":"Ministry of University and Research","award":["20225KH7BZ"],"award-info":[{"award-number":["20225KH7BZ"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:p>\n                    Tregs maintain immune tolerance through mechanisms tightly coupled to cellular metabolism. Whereas glycolysis supports migration of Tregs, lipid metabolism sustains their suppressive phenotype. Here, we identify SREBP1c as a central regulator of Treg immunobiology. Tregs from\n                    <jats:italic>Srebp1c<\/jats:italic>\n                    -deficient mice displayed impaired suppressive function, reduced frequencies in circulation and lymphoid tissues, and diminished expression of functional markers. These defects stemmed from intrinsic metabolic rewiring rather than systemic alterations, as both ex vivo Tregs (CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD25\n                    <jats:sup>hi<\/jats:sup>\n                    FoxP3\n                    <jats:sup>+<\/jats:sup>\n                    ) and in vitro\u2013derived Tregs lacking\n                    <jats:italic>Srebp1c<\/jats:italic>\n                    were shifted toward glycolysis. Integrated transcriptomic and lipidomic analyses revealed that\n                    <jats:italic>Srebp1c<\/jats:italic>\n                    -deficient Tregs exhibited defective phospholipid remodeling, with an accumulation of lysophosphatidylcholines over phosphatidylcholines, which we attributed to enhanced cytosolic phospholipase A2 (cPLA2\u03b1) activity and disruption of the Lands cycle. Altered lipid composition impaired adenosine-mediated immunosuppression by reducing CD73 expression and extracellular adenosine generation. Accordingly, pharmacological inhibition of cPLA2\u03b1 restored adenosine signaling, CD73 expression, and Treg suppressive capacity. Thus, by preserving phospholipid homeostasis, SREBP1c functions as an immunometabolic checkpoint that links lipid metabolism to adenosine-dependent Treg suppression.\n                  <\/jats:p>","DOI":"10.1172\/jci201325","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T16:00:36Z","timestamp":1784649636000},"source":"Crossref","is-referenced-by-count":0,"title":["SREBP1c modulates Treg immunobiology through a phospholipid-dependent adenosine pathway"],"prefix":"10.1172","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2611-1177","authenticated-orcid":true,"given":"Fabrizia","family":"Bonacina","sequence":"first","affiliation":[{"name":"Department of Excellence of Pharmacological and Biomolecular Sciences \u201cRodolfo Paoletti,\u201d Universit\u00e0 degli Studi di Milano, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Procaccini","sequence":"additional","affiliation":[{"name":"Laboratorio di Immunologia, Istituto degli Endotipi in Oncologia, Metabolismo e Immunologia \u201cG. Salvatore\u201d \u2013 Consiglio Nazionale delle Ricerche, Napoli, Italy."},{"name":"Unit\u00e0 di Neuroimmunologia, IRCCS Fondazione Santa Lucia, Roma, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Iaia","sequence":"additional","affiliation":[{"name":"Department of Excellence of Pharmacological and Biomolecular Sciences \u201cRodolfo Paoletti,\u201d Universit\u00e0 degli Studi di Milano, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Moretti","sequence":"additional","affiliation":[{"name":"Department of Excellence of Pharmacological and Biomolecular Sciences \u201cRodolfo Paoletti,\u201d Universit\u00e0 degli Studi di Milano, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Svecla","sequence":"additional","affiliation":[{"name":"Deutsches Herzzentrum der Charit\u00e9 \u2013 Charit\u00e9-Universit\u00e4tsmedizin, Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Pedretti","sequence":"additional","affiliation":[{"name":"Department of Excellence of Pharmacological and Biomolecular Sciences \u201cRodolfo Paoletti,\u201d Universit\u00e0 degli Studi di Milano, Milan, Italy."},{"name":"Istituto Europeo di Oncologia, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen","family":"Bogie","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infection, Hasselt University, Diepenbeek, Belgium."},{"name":"University MS Center, Pelt, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni Battista","family":"Vingiani","sequence":"additional","affiliation":[{"name":"Department of Excellence of Pharmacological and Biomolecular Sciences \u201cRodolfo Paoletti,\u201d Universit\u00e0 degli Studi di Milano, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Moregola","sequence":"additional","affiliation":[{"name":"Department of Excellence of Pharmacological and Biomolecular Sciences \u201cRodolfo Paoletti,\u201d Universit\u00e0 degli Studi di Milano, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Genova","sequence":"additional","affiliation":[{"name":"Department of Excellence of Pharmacological and Biomolecular Sciences \u201cRodolfo Paoletti,\u201d Universit\u00e0 degli Studi di Milano, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Russo","sequence":"additional","affiliation":[{"name":"Laboratorio di Immunologia, Istituto degli Endotipi in Oncologia, Metabolismo e Immunologia \u201cG. Salvatore\u201d \u2013 Consiglio Nazionale delle Ricerche, Napoli, Italy."},{"name":"Dipartimento Assistenziale Integrato de Medicina di Laboratorio e Trasfusionale, Azienda Ospedaliera Universitaria \u201cFederico II,\u201d Napoli, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giusy","family":"De Rosa","sequence":"additional","affiliation":[{"name":"Laboratorio di Immunologia, Istituto degli Endotipi in Oncologia, Metabolismo e Immunologia \u201cG. Salvatore\u201d \u2013 Consiglio Nazionale delle Ricerche, Napoli, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"La Rocca","sequence":"additional","affiliation":[{"name":"Laboratorio di Immunologia, Istituto degli Endotipi in Oncologia, Metabolismo e Immunologia \u201cG. 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