{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:57:26Z","timestamp":1790384246783,"version":"4.1.0"},"reference-count":45,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T00:00:00Z","timestamp":1735603200000},"content-version":"unspecified","delay-in-days":30,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"grant-in-aid for scientific research","award":["19K08900"],"award-info":[{"award-number":["19K08900"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2024,11,26]]},"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To elucidate the association between the changes in intracellular metabolism in the early stage of B cell activation and systemic lupus erythematosus (SLE) pathogenesis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>CD19<jats:sup>+<\/jats:sup> or CD19<jats:sup>+<\/jats:sup>CD27<jats:sup>-<\/jats:sup> (na\u00efve) cells from the peripheral blood of healthy controls and lupus patients were cultured under different stimuli. The changes in intracellular metabolism and signalling pathways in these cells were evaluated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Stimulation with CpG (Toll-like receptor 9 (TLR9) ligand) in vitro induced enhanced interleukin 21 (IL-21) receptor expression in CD19<jats:sup>+<\/jats:sup>CD27<jats:sup>-<\/jats:sup> cells after 24\u2009hours. The addition of IL-21 to the CpG stimulation enhanced the extracellular acidification rate, which indicates glycolysis, within 30\u2009min. IL-21 receptor (IL-21R) expression induced by CpG stimulation was selectively inhibited by 2-deoxy-D-glucose (hexokinase 2 (HK2) inhibitor) and heptelidic acid (glyceraldehyde 3-phosphate dehydrogenase (GAPDH) inhibitor). RNA immunoprecipitation with anti-GAPDH antibody revealed that CpG stimulation dissociated the binding between IL-21R messenger RNA (mRNA) and GAPDH under no stimulation. HK2 and GAPDH expression were higher in CD19<jats:sup>+<\/jats:sup>CD27<jats:sup>-<\/jats:sup> cells of lupus patients than in those of healthy controls, and GAPDH expression was correlated with the plasmocyte count and disease activity score.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>IL-21R mRNA-GAPDH binding dissociation associated with rapid glycolytic enhancement by the TLR9 ligand in B cells may induce plasmocyte differentiation through IL-21 signals and be involved in exacerbating SLE.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/rmdopen-2024-004567","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T11:35:24Z","timestamp":1735644924000},"page":"e004567","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Induction of interleukin 21 receptor expression via 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