title: Regulation of dendritic cell maturation and function by Bruton's tyrosine kinase via IL-10 and Stat3.
abstract: Btk plays crucial roles in the differentiation and activation of B and myeloid cells. Despite drastic reductions of other Ig isotypes, paradoxically high IgE responses have been known in btk mutant mice. Here we show that btk(-/-) dendritic cells exhibit a more mature phenotype and a stronger in vitro and in vivo T cell-stimulatory ability than wild-type cells. Increased IgE responses were induced by adoptive transfer of btk(-/-) dendritic cells into mice. Consistent with the stronger T cell-stimulatory ability of btk(-/-) dendritic cells, btk(-/-) mice exhibited enhanced inflammation in Th2-driven asthma and Th1-driven contact sensitivity experiments. These negative regulatory functions of Btk in dendritic cells appear to be mediated mainly through autocrine secretion of IL-10 and subsequent activation of Stat3.
authors.affiliation: Divisions of Cell Biology and Molecular Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kawakami
authors.forename: Naoki
authors.initials: N
authors.lastname: Inagaki
authors.forename: Shahram
authors.initials: S
authors.lastname: Salek-Ardakani
authors.forename: Jiro
authors.initials: J
authors.lastname: Kitaura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Koichi
authors.initials: K
authors.lastname: Nagao
authors.forename: Yu
authors.initials: Y
authors.lastname: Kawakami
authors.forename: Wenbin
authors.initials: W
authors.lastname: Xiao
authors.forename: Hiroichi
authors.initials: H
authors.lastname: Nagai
authors.forename: Michael
authors.initials: M
authors.lastname: Croft
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kawakami
mesh_terms: D019264:Adoptive Transfer; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D001249:Asthma / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D003877:Dermatitis, Contact / Q000276:immunology; D007114:Immunization; D015151:Immunoblotting; D007073:Immunoglobulin E / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000276:immunology / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D016753:Interleukin-10; D007073:Immunoglobulin E; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625951:Btk protein, mouse