{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T01:27:12Z","timestamp":1793582832886,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100007877","name":"Fujita Health University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007877","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2026,9,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Monosaccharides are fundamental biomolecules involved in various biological processes. Rare sugars, naturally scarce monosaccharide derivatives, exhibit unique physiological effects independent of standard energy metabolism. Among them, d\u2010sorbose, the C\u20103 epimer of d\u2010fructose, has poorly understood biological functions. This study investigated the immunometabolic effects of d\u2010sorbose, focusing on regulatory T\u2010cell (Treg) differentiation and immune modulation. Ex\u00a0vivo assays using splenic na\u00efve CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells revealed that d\u2010sorbose significantly increased Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    Treg frequencies to levels comparable to d\u2010mannose, without inducing the CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell reduction observed with d\u2010mannose. In\u00a0vivo, continuous d\u2010sorbose administration ameliorated ovalbumin\u2010induced airway inflammation and prevented autoimmune diabetes in non\u2010obese diabetic mice by selectively increasing interleukin\u201010\u2010producing Tregs in regional lymph nodes and inflamed tissues. Histological analyses revealed reduced inflammatory cell infiltration and preserved tissue architecture in d\u2010sorbose\u2010treated groups. Metabolomic profiling indicated that d\u2010sorbose suppressed glycolysis, the pentose phosphate pathway, and the hexosamine biosynthetic pathway (HBP), as evidenced by decreased UDP\u2010GlcNAc levels, while elevating the tricarboxylic acid cycle intermediate malate. Pharmacological inhibition of glutamine\u2013fructose\u20106\u2010phosphate aminotransferase, combined with glutamine restriction and GlcNAc rescue assays, demonstrated that d\u2010sorbose promotes Treg differentiation through coordinated metabolic reprogramming of glucose partitioning and glutamine catabolism rather than passive HBP inhibition. Notably, d\u2010sorbose treatment did not alter T\u2010cell survival and demonstrated a favorable safety profile during long\u2010term administration. These findings identify d\u2010sorbose as a novel immunoregulatory sugar that promotes functional Treg differentiation by orchestrating intracellular glucose and glutamine metabolism, highlighting its potential as a dietary or therapeutic agent for controlling inflammatory and autoimmune diseases.\n                  <\/jats:p>","DOI":"10.1096\/fj.202601110r","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T16:05:31Z","timestamp":1787933131000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["d\u2010Sorbose Promotes Regulatory T\u2010Cell Differentiation and Ameliorates Autoimmune and Allergic Diseases via Hexosamine Biosynthetic Pathway Inhibition"],"prefix":"10.1096","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7636-4481","authenticated-orcid":false,"given":"Fumiaki","family":"Sato","sequence":"first","affiliation":[{"name":"Department of Disease Systems Analysis Medicine Fujita Health University School of Medical Sciences  Toyoake Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6260-8300","authenticated-orcid":false,"given":"Masato","family":"Hoshi","sequence":"additional","affiliation":[{"name":"Department of Disease Systems Analysis Medicine Fujita Health University School of Medical Sciences  Toyoake Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2126-817X","authenticated-orcid":false,"given":"Hiroyuki","family":"Yokoi","sequence":"additional","affiliation":[{"name":"Department of Disease Systems Analysis Medicine Fujita Health University School of Medical Sciences  Toyoake Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2554-1348","authenticated-orcid":false,"given":"Sayaka","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Disease Systems Analysis Medicine Fujita Health University School of Medical Sciences  Toyoake Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4553-1217","authenticated-orcid":false,"given":"Ryosuke","family":"Takenaka","sequence":"additional","affiliation":[{"name":"Department of Disease Systems Analysis Medicine Fujita Health University School of Medical Sciences  Toyoake Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5728-319X","authenticated-orcid":false,"given":"Nao","family":"Shimoga","sequence":"additional","affiliation":[{"name":"Department of Disease Systems Analysis Medicine Fujita Health University School of Medical Sciences  Toyoake Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4656-7124","authenticated-orcid":false,"given":"Nanaka","family":"Morita","sequence":"additional","affiliation":[{"name":"Department of Medical Science Technology, School of Health Science at Narita International University of Health and Welfare  Narita Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4124-3581","authenticated-orcid":false,"given":"Chieko","family":"Tashita","sequence":"additional","affiliation":[{"name":"Department of Medical Technology Gifu University of Medical Science  Seki Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6803-2011","authenticated-orcid":false,"given":"Kyoka","family":"Yamazaki","sequence":"additional","affiliation":[{"name":"Research and Development Matsutani Chemical Industry Co. 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