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Tyrosine kinase Btk is required for NK cell activation
- Source :
- The Journal of biological chemistry. 287(28)
- Publication Year :
- 2012
-
Abstract
- Bruton 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.<br />link_to_subscribed_fulltext
- Subjects :
- Antigens, Differentiation, T-Lymphocyte
Cell Survival
Immunology
Immunoblotting
chemical and pharmacologic phenomena
Lymphocyte Activation
Biochemistry
Granzymes
Interferon-gamma
Mice
Immune system
immune system diseases
Agammaglobulinemia
Antigens, CD
Lysosomal-Associated Membrane Protein 1
hemic and lymphatic diseases
medicine
Agammaglobulinaemia Tyrosine Kinase
Bruton's tyrosine kinase
Cytotoxic T cell
Animals
Humans
Interferon gamma
Lectins, C-Type
Molecular Biology
Cells, Cultured
Mice, Knockout
Innate immune system
biology
Perforin
Genetic Diseases, X-Linked
Cell Biology
Protein-Tyrosine Kinases
Flow Cytometry
Adoptive Transfer
Immunity, Innate
Cell biology
Toll-Like Receptor 3
Killer Cells, Natural
Mice, Inbred C57BL
Poly I-C
Granzyme
biology.protein
Additions and Corrections
Chemical and Drug Induced Liver Injury
Tyrosine kinase
medicine.drug
Subjects
Details
- ISSN :
- 1083351X
- Volume :
- 287
- Issue :
- 28
- Database :
- OpenAIRE
- Journal :
- The Journal of biological chemistry
- Accession number :
- edsair.doi.dedup.....cb6de40a9d47bd862e6f9f47245bd59b