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Article: Tyrosine kinase Btk is required for NK cell activation

TitleTyrosine kinase Btk is required for NK cell activation
Authors
Issue Date2012
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal Of Biological Chemistry, 2012, v. 287 n. 28, p. 23769-23778 How to Cite?
AbstractBruton tyrosine kinase (Btk) is not only critical for B cell development and differentiation but is also involved in the regulation of Toll-like receptor-triggered innate response of macrophages. However, whether Btk is involved in the regulation of natural killer (NK) cell innate function remains unknown. Here, we show that Btk expression is up-regulated during maturation and activation of mouse NK cells. Murine Btk -/-NKcells have decreased innate immune responses to the TLR3 ligand, with reduced expressions of IFN-γ, perforin, and granzyme-B and decreased cytotoxic activity. Furthermore, Btk is found to promote TLR3-triggered NK cell activation mainly by activating the NF-κB pathway. Poly(I:C)-induced NK cell-mediated acute hepatitis was observed to be attenuated in Btk -/- mice or the mice with in vivo administration of the Btk inhibitor. Correspondingly, liver damage was aggravated in Btk -/- mice after the adoptive transfer of Btk +/+ NK cells, further indicating that Btk-mediated NK cell activation contributes to TLR3-triggered acute liver injury. Importantly, reduced TLR3-triggered activation of human NK cells was observed in Btk-deficient patients with X-linked agammaglobulinemia, as evidenced by the reduced IFN-γ, CD69, and CD107a expression and cytotoxic activity. These results indicate that Btk is required for activation of NK cells, thus providing insight into the physiological significance of Btk in the regulation of immune cell functions and innate inflammatory response. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/152790
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorBao, Yen_HK
dc.contributor.authorZheng, Jen_HK
dc.contributor.authorHan, Cen_HK
dc.contributor.authorJin, Jen_HK
dc.contributor.authorHan, Hen_HK
dc.contributor.authorLiu, Yen_HK
dc.contributor.authorLau, YLen_HK
dc.contributor.authorTu, Wen_HK
dc.contributor.authorCao, Xen_HK
dc.date.accessioned2012-07-16T09:48:35Z-
dc.date.available2012-07-16T09:48:35Z-
dc.date.issued2012en_HK
dc.identifier.citationJournal Of Biological Chemistry, 2012, v. 287 n. 28, p. 23769-23778en_HK
dc.identifier.issn0021-9258en_HK
dc.identifier.urihttp://hdl.handle.net/10722/152790-
dc.description.abstractBruton tyrosine kinase (Btk) is not only critical for B cell development and differentiation but is also involved in the regulation of Toll-like receptor-triggered innate response of macrophages. However, whether Btk is involved in the regulation of natural killer (NK) cell innate function remains unknown. Here, we show that Btk expression is up-regulated during maturation and activation of mouse NK cells. Murine Btk -/-NKcells have decreased innate immune responses to the TLR3 ligand, with reduced expressions of IFN-γ, perforin, and granzyme-B and decreased cytotoxic activity. Furthermore, Btk is found to promote TLR3-triggered NK cell activation mainly by activating the NF-κB pathway. Poly(I:C)-induced NK cell-mediated acute hepatitis was observed to be attenuated in Btk -/- mice or the mice with in vivo administration of the Btk inhibitor. Correspondingly, liver damage was aggravated in Btk -/- mice after the adoptive transfer of Btk +/+ NK cells, further indicating that Btk-mediated NK cell activation contributes to TLR3-triggered acute liver injury. Importantly, reduced TLR3-triggered activation of human NK cells was observed in Btk-deficient patients with X-linked agammaglobulinemia, as evidenced by the reduced IFN-γ, CD69, and CD107a expression and cytotoxic activity. These results indicate that Btk is required for activation of NK cells, thus providing insight into the physiological significance of Btk in the regulation of immune cell functions and innate inflammatory response. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.en_HK
dc.languageengen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_HK
dc.relation.ispartofJournal of Biological Chemistryen_HK
dc.titleTyrosine kinase Btk is required for NK cell activationen_HK
dc.typeArticleen_HK
dc.identifier.emailLau, YL:lauylung@hkucc.hku.hken_HK
dc.identifier.emailTu, W:wwtu@hkucc.hku.hken_HK
dc.identifier.authorityLau, YL=rp00361en_HK
dc.identifier.authorityTu, W=rp00416en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1074/jbc.M112.372425en_HK
dc.identifier.pmid22589540-
dc.identifier.pmcidPMC3390651-
dc.identifier.scopuseid_2-s2.0-84863609982en_HK
dc.identifier.hkuros200709en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84863609982&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume287en_HK
dc.identifier.issue28en_HK
dc.identifier.spage23769en_HK
dc.identifier.epage23778en_HK
dc.identifier.isiWOS:000306511300047-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridBao, Y=55085062200en_HK
dc.identifier.scopusauthoridZheng, J=55217878700en_HK
dc.identifier.scopusauthoridHan, C=7403379834en_HK
dc.identifier.scopusauthoridJin, J=55230693100en_HK
dc.identifier.scopusauthoridHan, H=12793759900en_HK
dc.identifier.scopusauthoridLiu, Y=25632591500en_HK
dc.identifier.scopusauthoridLau, YL=7201403380en_HK
dc.identifier.scopusauthoridTu, W=7006479236en_HK
dc.identifier.scopusauthoridCao, X=7403370836en_HK

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