Regulation of dendritic cell maturation and function by Bruton's tyrosine kinase via IL-10 and Stat3.

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. [ABSTRACT FROM AUTHOR]