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.

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 acti...

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Autores principales:	Yan-Feng Li, Koon-Guan Lee, Xijun Ou, Kong-Peng Lam
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7979325d10f04aa5b4d841925ed93979
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spelling	oai:doaj.org-article:7979325d10f04aa5b4d841925ed939792021-11-25T06:02:31ZBruton'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.1932-620310.1371/journal.pone.0105420https://doaj.org/article/7979325d10f04aa5b4d841925ed939792014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25170774/?tool=EBIhttps://doaj.org/toc/1932-6203Stimulation 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.Yan-Feng LiKoon-Guan LeeXijun OuKong-Peng LamPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 8, p e105420 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yan-Feng Li Koon-Guan Lee Xijun Ou Kong-Peng Lam 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.
description	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.
format	article
author	Yan-Feng Li Koon-Guan Lee Xijun Ou Kong-Peng Lam
author_facet	Yan-Feng Li Koon-Guan Lee Xijun Ou Kong-Peng Lam
author_sort	Yan-Feng Li
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.
title_short	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.
title_full	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.
title_fullStr	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.
title_full_unstemmed	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.
title_sort	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.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/7979325d10f04aa5b4d841925ed93979
work_keys_str_mv	AT yanfengli brutonstyrosinekinaseandproteinkinasecμarerequiredfortlr79inducedikkaandirf1activationandinterferonbproductioninconventionaldendriticcells AT koonguanlee brutonstyrosinekinaseandproteinkinasecμarerequiredfortlr79inducedikkaandirf1activationandinterferonbproductioninconventionaldendriticcells AT xijunou brutonstyrosinekinaseandproteinkinasecμarerequiredfortlr79inducedikkaandirf1activationandinterferonbproductioninconventionaldendriticcells AT kongpenglam brutonstyrosinekinaseandproteinkinasecμarerequiredfortlr79inducedikkaandirf1activationandinterferonbproductioninconventionaldendriticcells
_version_	1718414290677923840

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.

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