title: Bruton's tyrosine kinase and protein kinase C µ are required for TLR7/9-induced IKKα and IRF-1 activation and interferon-β production in conventional dendritic cells.
abstract: Stimulation of TLR7/9 by their respective ligands leads to the activation of IκB kinase α (IKKα) and Interferon Regulatory Factor 1 (IRF-1) and results in interferon (IFN)-β production in conventional dendritic cells (cDC). However, which other signaling molecules are involved in IKKα and IRF-1 activation during TLR7/9 signaling pathway are not known. We and others have shown that Bruton's Tyrosine Kinase (BTK) played a part in TLR9-mediated cytokine production in B cells and macrophages. However, it is unclear if BTK participates in TLR7/9-induced IFN-β production in cDC. In this study, we show that BTK is required for IFN-β synthesis in cDC upon TLR7/9 stimulation and that stimulated BTK-deficient cDC are defective in the induction of IKKα/β phosphorylation and IRF-1 activation. In addition, we demonstrate that Protein Kinase C µ (PKCµ) is also required for TLR7/9-induced IRF-1 activation and IFN-β upregulation in cDC and acts downstream of BTK. Taken together, we have uncovered two new molecules, BTK and PKCµ, that are involved in TLR7/9-triggered IFN-β production in cDC.
authors.affiliation: Immunology Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore, Singapore.
authors.forename: Yan-Feng
authors.initials: YF
authors.lastname: Li
authors.affiliation: Immunology Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore, Singapore.
authors.forename: Koon-Guan
authors.initials: KG
authors.lastname: Lee
authors.affiliation: Immunology Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore, Singapore.
authors.forename: Xijun
authors.initials: X
authors.lastname: Ou
authors.affiliation: Immunology Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Kong-Peng
authors.initials: KP
authors.lastname: Lam
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D017353:Gene Deletion; D051550:I-kappa B Kinase / Q000276:immunology*; D050856:Interferon Regulatory Factor-1 / Q000276:immunology*; D016899:Interferon-beta / Q000276:immunology*; D008810:Mice, Inbred C57BL; D011493:Protein Kinase C / Q000276:immunology*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000276:immunology*
chemical_list: D050856:Interferon Regulatory Factor-1; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; D016899:Interferon-beta; C089212:protein kinase D; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625951:Btk protein, mouse; D051550:I-kappa B Kinase; D011493:Protein Kinase C