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Development and Functional Characterization of Murine Tolerogenic Dendritic Cells
09:51

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Published on: May 18, 2018

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

Yuko Kawakami1, Naoki Inagaki, Shahram Salek-Ardakani

  • 1Divisions of Cell Biology and Molecular Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA.

Proceedings of the National Academy of Sciences of the United States of America
|December 24, 2005
PubMed

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.

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