{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:02:41Z","timestamp":1791838961611,"version":"4.3.4"},"reference-count":60,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"786","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2025,2,19]]},"abstract":"<jats:p>\n            Systemic lupus erythematosus (SLE) is characterized by dysfunctional regulatory T cells (T\n            <jats:sub>regs<\/jats:sub>\n            ). We previously showed that protein phosphatase 2A (PP2A) plays a critical role in maintaining the suppressive function of T\n            <jats:sub>regs<\/jats:sub>\n            . Here, we analyzed phosphoproteomics and metabolomics data from PP2A\u2013wild type and PP2A-deficient T\n            <jats:sub>regs<\/jats:sub>\n            and demonstrated that PP2A regulates T\n            <jats:sub>reg<\/jats:sub>\n            function through the pentose phosphate pathway (PPP). Furthermore, we proved that the PPP metabolite gluconolactone (GDL) enhances in vitro induced (i)T\n            <jats:sub>reg<\/jats:sub>\n            differentiation and function by promoting forkhead box protein 3 and phosphorylated signal transducer and activator of transcription 5 expression and inhibits T helper 17 (T\n            <jats:sub>H<\/jats:sub>\n            17) differentiation in murine cells. In short-term imiquimod-induced autoimmunity in mice, treatment with GDL alleviates inflammation by inhibiting T\n            <jats:sub>H<\/jats:sub>\n            17 cells. GDL promotes T\n            <jats:sub>regs<\/jats:sub>\n            function and alleviates skin lesions in MRL.\n            <jats:italic>lpr<\/jats:italic>\n            lupus-prone mice in vivo. It also promotes T\n            <jats:sub>regs<\/jats:sub>\n            differentiation and function in ex vivo experiments using cells from patients with SLE. Last, in patients suffering from cutaneous lupus erythematosus, topical application of a GDL-containing cream controlled skin inflammation and improved the clinical and histologic appearance of the skin lesions within 2 weeks. Together, we have identified GDL as a PPP metabolite and showed mechanistically that it restores immune regulation in vitro and in vivo by inducing T\n            <jats:sub>reg<\/jats:sub>\n            suppressive function and inhibiting T\n            <jats:sub>H<\/jats:sub>\n            17 cells. GDL should be considered as a treatment approach for inflammatory and autoimmune diseases.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.adp4447","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T18:58:27Z","timestamp":1739991507000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":17,"title":["Gluconolactone restores immune regulation and alleviates skin inflammation in lupus-prone mice and in patients with cutaneous lupus"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4681-4923","authenticated-orcid":true,"given":"Wei","family":"Li","sequence":"first","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3897-4578","authenticated-orcid":true,"given":"Antonios G. A.","family":"Kolios","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA."},{"name":"Department of Dermatology, University of Zurich, Raemistrasse 100, 8091 Zurich, Switzerland."},{"name":"Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5965-2126","authenticated-orcid":true,"given":"Wenliang","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalina","family":"Burbano","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5319-3174","authenticated-orcid":true,"given":"Kohei","family":"Karino","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7237-1954","authenticated-orcid":true,"given":"Theodoros","family":"Vichos","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6145-5947","authenticated-orcid":true,"given":"Morgane","family":"Humbel","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasileios C.","family":"Kyttaris","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8072-1358","authenticated-orcid":true,"given":"Maria G.","family":"Tsokos","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9589-2360","authenticated-orcid":true,"given":"George C.","family":"Tsokos","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, 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comparative study in efficacy and safety of 0.1% tacrolimus and 0.05% clobetasol propionate ointment in discoid lupus erythematosus by modified cutaneous lupus erythematosus disease area and severity index","volume":"95","author":"Pothinamthong P.","year":"2012","unstructured":"P. Pothinamthong, P. Janjumratsang, A comparative study in efficacy and safety of 0.1% tacrolimus and 0.05% clobetasol propionate ointment in discoid lupus erythematosus by modified cutaneous lupus erythematosus disease area and severity index. J. Med. Assoc. Thai. 95, 933\u2013940 (2012).","journal-title":"J. Med. Assoc. 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