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http://purl.uniprot.org/citations/25724205http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/25724205http://www.w3.org/2000/01/rdf-schema#comment"

Objective

B cells play an important role in the pathogenesis of autoimmune diseases. The role of Bruton's tyrosine kinase (Btk) in cytokine-induced human B cell differentiation and class-switch recombination remains incompletely defined. This study analysed the effect of Btk on human activated B cells.

Methods

Purified B cells from healthy subjects were stimulated with B cell receptor (BCR) and other stimuli with or without a Btk inhibitor and gene expression was measured. The B cell line BJAB was used to assess Btk-associated signalling cascades. Phosphorylated Btk (p-Btk) in peripheral blood B cells obtained from 10 healthy subjects and 41 patients with RA was measured by flow cytometry and compared with patient backgrounds.

Results

IL-21 signalling, in concert with BCR, CD40 and BAFF signals, led to robust expression of differentiation- and class-switch DNA recombination-related genes and IgG production in human B cells, all of which were significantly suppressed by the Btk inhibitor. Although phosphorylation of STAT1 and STAT3 was induced by co-stimulation with IL-21, BCR and CD40, STAT1 phosphorylation in the nucleus, but not in the cytoplasm, was exclusively impaired by Btk blockade. High levels of p-Btk were noted in B cells of RA patients compared with controls and they correlated significantly with titres of RF among RF-positive patients.

Conclusion

The findings elucidate a model in which Btk not only plays a fundamental role in the regulation of BCR signalling, but may also mediate crosstalk with cytokine signalling pathways through regulation of IL-21-induced phosphorylation of STAT1 in the nuclei of human B cells. Btk appears to have pathological relevance in RA."xsd:string
http://purl.uniprot.org/citations/25724205http://purl.org/dc/terms/identifier"doi:10.1093/rheumatology/keu532"xsd:string
http://purl.uniprot.org/citations/25724205http://purl.uniprot.org/core/author"Yoshikawa M."xsd:string
http://purl.uniprot.org/citations/25724205http://purl.uniprot.org/core/author"Kubo S."xsd:string
http://purl.uniprot.org/citations/25724205http://purl.uniprot.org/core/author"Kondo M."xsd:string
http://purl.uniprot.org/citations/25724205http://purl.uniprot.org/core/author"Tanaka Y."xsd:string
http://purl.uniprot.org/citations/25724205http://purl.uniprot.org/core/author"Iwata S."xsd:string
http://purl.uniprot.org/citations/25724205http://purl.uniprot.org/core/author"Wang S.P."xsd:string
http://purl.uniprot.org/citations/25724205http://purl.uniprot.org/core/author"Niiro H."xsd:string
http://purl.uniprot.org/citations/25724205http://purl.uniprot.org/core/author"Nakayamada S."xsd:string
http://purl.uniprot.org/citations/25724205http://purl.uniprot.org/core/author"Jabbarzadeh-Tabrizi S."xsd:string
http://purl.uniprot.org/citations/25724205http://purl.uniprot.org/core/date"2015"xsd:gYear
http://purl.uniprot.org/citations/25724205http://purl.uniprot.org/core/name"Rheumatology (Oxford)"xsd:string
http://purl.uniprot.org/citations/25724205http://purl.uniprot.org/core/pages"1488-1497"xsd:string
http://purl.uniprot.org/citations/25724205http://purl.uniprot.org/core/title"Amplification of IL-21 signalling pathway through Bruton's tyrosine kinase in human B cell activation."xsd:string
http://purl.uniprot.org/citations/25724205http://purl.uniprot.org/core/volume"54"xsd:string
http://purl.uniprot.org/citations/25724205http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/25724205
http://purl.uniprot.org/citations/25724205http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/25724205
http://purl.uniprot.org/uniprot/#_Q06187-mappedCitation-25724205http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25724205
http://purl.uniprot.org/uniprot/#_Q3MS86-mappedCitation-25724205http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25724205
http://purl.uniprot.org/uniprot/#_Q3MS87-mappedCitation-25724205http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25724205
http://purl.uniprot.org/uniprot/#_Q3MS88-mappedCitation-25724205http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25724205
http://purl.uniprot.org/uniprot/#_Q3MS89-mappedCitation-25724205http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25724205
http://purl.uniprot.org/uniprot/#_Q3MS90-mappedCitation-25724205http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25724205
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