{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:15:40Z","timestamp":1787026540398,"version":"build-2736575974"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T00:00:00Z","timestamp":1726531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\u03b1-galactosylceramide (\u03b1-GalCer), a prototypical agonist of invariant natural killer T (iNKT) cells, stimulates iNKT cells to produce various cytokines such as IFN\u03b3 and IL4. Moreover, repeated \u03b1-GalCer treatment can cause protective or pathogenic outcomes in various immune-mediated diseases. However, the precise role of \u03b1-GalCer-activated iNKT cells in sepsis development remains unclear. To address this issue, we employed a lipopolysaccharide (LPS)\/D-galactosamine (D-GalN)-induced murine sepsis model and two alternative models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Sepsis was induced in wild-type (WT) C57BL\/6 (B6) mice by three methods (LPS\/D-GalN, \u03b1-GalCer\/D-GalN, and cecal slurry), and these mice were monitored for survival rates. WT B6 mice were intraperitoneally injected with \u03b1-GalCer or OCH (an IL4-biased \u03b1-GalCer analog) one week prior to the induction of sepsis. To investigate the effects of \u03b1-GalCer-mediated iNKT cell activation on sepsis development, immune responses were analyzed by flow cytometry using splenocytes and liver-infiltrating leukocytes. In addition, a STAT6 inhibitor (AS1517499) and an IL10 inhibitor (AS101) were employed to evaluate the involvement of IL4 or IL10 signaling. Furthermore, we performed B cell adoptive transfers to examine the contribution of \u03b1-GalCer-induced regulatory B (Breg) cell populations in sepsis protection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In vivo<\/jats:italic>\n                      \u03b1-GalCer pretreatment polarized iNKT cells towards IL4- and IL10-producing phenotypes, significantly attenuating LPS\/D-GalN-induced septic lethality in WT B6 mice. Furthermore, \u03b1-GalCer pretreatment reduced the infiltration of immune cells to the liver and attenuated pro-inflammatory cytokine production. Treatment with a STAT6 inhibitor was unable to modulate disease progression, indicating that IL4 signaling did not significantly affect iNKT cell-mediated protection against sepsis. This finding was confirmed by pretreatment with OCH, which did not alter sepsis outcomes. However, interestingly, prophylactic effects of \u03b1-GalCer on sepsis were significantly suppressed by treatment with an IL10 antagonist, suggesting induction of IL10-dependent anti-inflammatory responses. In addition to IL10-producing iNKT cells, IL10-producing B cell populations were significantly increased after \u03b1-GalCer pretreatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Overall, our results identify \u03b1-GalCer-mediated induction of IL10 by iNKT and B cells as a promising option for controlling the pathogenesis of postoperative sepsis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2024.1457690","type":"journal-article","created":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T08:41:45Z","timestamp":1726648905000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["The iNKT cell ligand \u03b1-GalCer prevents murine septic shock by inducing IL10-producing iNKT and B cells"],"prefix":"10.3389","volume":"15","author":[{"given":"Yun 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