biostudies-literatureMarongiu LAssociazione Italiana per la Ricerca sul CancroIntramural NIH HHSCourant Forschungszentrum Geobiologie, Georg-August-Universität GöttingenNIDDK NIH HHSNew York University School of MedicineTeikyo University School of MedicineNIAID NIH HHSMinistry of Health, UgandaNew York UniversityNational Institutes of HealthCrohn’s and Colitis Foundation of AmericaUniHealth Foundationeaaz2120https://www.ebi.ac.uk/biostudies/studies/S-EPMC8091591biostudies-literatureUnknown14(676)Innate immune responses to Gram-negative bacteria depend on the recognition of lipopolysaccharide (LPS) by a receptor complex that includes CD14 and TLR4. In dendritic cells (DCs), CD14 enhances the activation not only of TLR4 but also that of the NFAT family of transcription factors, which suppresses cell survival and promotes the production of inflammatory mediators. NFAT activation requires Ca²⁺ mobilization. In DCs, Ca²⁺ mobilization in response to LPS depends on phospholipase C γ2 (PLCγ2), which produces inositol 1,4,5-trisphosphate (IP₃). Here, we showed that the IP₃ receptor 3 (IP₃R3) and ITPKB, a kinase that converts IP₃ to inositol 1,3,4,5-tetrakisphosphate (IP₄), were both necessary for Ca²⁺ mScience signalingInositol 1,4,5-trisphosphate 3-kinase B promotes Ca²⁺ mobilization and the inflammatory activity of dendritic cells.PMC8091591Z01 ES08004612/2018RF-2018-123670721R01AI121066-01A1IG 2019IHDDC P30 DK034854R01 AI121066P30 DK034854IG 2019Id.2351223512Garre MMorii TZanoni ICatelani TProsperi DRotem RShears SGranucci FMingozzi FMarongiu LCigni CSironi LSchurmans SCollini MSakaguchi RMarzi RDi Gioia MMoro MCrosti MColombo MParazzoli DfalseInositol 1,4,5-trisphosphate 3-kinase B promotes Ca²⁺ mobilization and the inflammatory activity of dendritic cells.Innate immune responses to Gram-negative bacteria depend on the recognition of lipopolysaccharide (LPS) by a receptor complex that includes CD14 and TLR4. In dendritic cells (DCs), CD14 enhances the activation not only of TLR4 but also that of the NFAT family of transcription factors, which suppresses cell survival and promotes the production of inflammatory mediators. NFAT activation requires Ca²⁺ mobilization. In DCs, Ca²⁺ mobilization in response to LPS depends on phospholipase C γ2 (PLCγ2), which produces inositol 1,4,5-trisphosphate (IP₃). Here, we showed that the IP₃ receptor 3 (IP₃R3) and ITPKB, a kinase that converts IP₃ to inositol 1,3,4,5-tetrakisphosphate (IP₄), were both necessary for Ca²⁺ m2021-01-01T00:00:00Z2021 Mar2025-04-29T11:30:05.933Z2025-04-06T19:55:08.518ZS-EPMC80915913378561110.1126/scisignal.aaz2120