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Immunol."],"abstract":"<jats:p>Vitamin D<jats:sub>3<\/jats:sub> (VD<jats:sub>3<\/jats:sub>) participated widely in the nuclear factor-\u03baB (NF-\u03baB)-mediated inflammation, apoptosis, and autophagy through the vitamin D receptor (VDR). However, the molecular mechanisms remain not understood in teleost. The present study investigated the functions of VD<jats:sub>3<\/jats:sub>\/VDR on intestinal inflammation, autophagy, and apoptosis of turbot <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>. Triple replicates of 30 fish were fed with each of three diets with graded levels of 32.0 (D<jats:sub>0<\/jats:sub>), 1012.6 (D<jats:sub>1<\/jats:sub>), and 3978.2 (D<jats:sub>2<\/jats:sub>) IU\/kg VD<jats:sub>3<\/jats:sub>. Obvious intestinal enteritis was observed in the D<jats:sub>0<\/jats:sub> group and followed with dysfunction of intestinal mucosal barriers. The intestinal inflammatory response induced by VD<jats:sub>3<\/jats:sub> deficiency was regulated by the NF-\u03baB\/inflammasome signalling. The promotion of intestinal apoptosis and suppression of intestinal autophagy were also observed in the D<jats:sub>0<\/jats:sub> group. Similarly, VD<jats:sub>3<\/jats:sub> deficiency <jats:italic>in vitro<\/jats:italic> induced more intense inflammation regulated by NF-\u03baB\/inflammasome signalling. The mutually exclusive apoptosis and autophagy were also observed in the group without 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub><jats:italic>in vitro<\/jats:italic>, accompanied by similar changes in apoptosis and autophagy increased apoptosis. The gene expression of VDRs was significantly increased with the increasing VD<jats:sub>3<\/jats:sub> supplementation both <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>. Moreover, VDR knockdown in turbot resulted in intestinal inflammation, and this process relied on the activation of inflammasome mediated by NF-\u03baB signalling. Simultaneously, intestinal apoptosis was promoted, whereas intestinal autophagy was inhibited. In conclusion, VD<jats:sub>3<\/jats:sub> deficiency could induce intestinal inflammation <jats:italic>via<\/jats:italic> activation of the NF-\u03baB\/inflammasome pathway, intestinal apoptosis, and autophagy formed a mutually exclusive relation in teleost. And VDR is the critical molecule in those processes.<\/jats:p>","DOI":"10.3389\/fimmu.2022.986593","type":"journal-article","created":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T10:25:07Z","timestamp":1662632707000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Vitamin D3 deficiency induced intestinal inflammatory response of turbot through nuclear factor-\u03baB\/inflammasome pathway, accompanied by the mutually exclusive apoptosis and 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