Characterization of the Role of Bruton`s Tyrosine Kinase (BTK) for Myeloid Cell Function in Mouse and Man

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Mutations within the gene coding for Bruton’s Tyrosine Kinase (BTK) cause X-linked agammaglobulinemia (XLA) in man, which is characterized by the almost complete absence of mature B cells within the circulation accompanied by the lack of immunoglobulins and therefore by a high susceptibility to recurrent bacterial infections. A recent study revealed that only 26% of 201 patients suffering from XLA were aged 21 years or older. However, BTK is expressed not exclusively in B cells but also in other hematopoietic cells including cells of the myeloid lineage but the impact of BTK to the function of XLA myeloid cells is discussed controversial. Recently, we have shown a profound maturation and functional defect of Btk-deficient neutrophilic granulocytes in mice. To get more insight into the role of BTK for the myeloid compartment we suggest here new attempts and approaches. Using in vivo experimental mouse models depending in a first line mainly on the action of myeloid cells, like the experimental autoimmune encephalomyelitis (EAE) or wound healing models, or human myeloid cells in which BTK expression or function will be down-modulated, and also “humanized mice” presenting human hematopoietic cells in which BTK expression will be knocked-down, we expect results that engross our knowledge about the role of Btk/BTK for myeloid cell development and function in mouse and man. Finally, these results may alter our understanding about the pathogenesis of XLA as well as therapy approaches for treatment of affected patients.