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

布鲁顿酪氨酸激酶（BTK）基因编码中的突变导致人类x连锁无球蛋白血症（XLA），其特征是循环中几乎完全缺乏成熟的B细胞，同时缺乏免疫球蛋白，因此对复发性细菌感染非常敏感。最近的一项研究显示，201名XLA患者中只有26%的人年龄在21岁或以上。然而，BTK不仅在B细胞中表达，也在包括髓系细胞在内的其他造血细胞中表达，但BTK对XLA髓系细胞功能的影响尚存争议。最近，我们在小鼠中发现了btk缺陷中性粒细胞的成熟和功能缺陷。为了更深入地了解BTK在髓系间室中的作用，我们在这里提出了新的尝试和方法。使用一线主要依赖髓细胞作用的体内实验小鼠模型，如实验性自身免疫性脑脊髓炎（EAE）或伤口愈合模型，或BTK表达或功能下调的人髓细胞，以及BTK表达下调的人造血细胞的“人源化小鼠”，我们期望得到的结果能够深入了解Btk/ Btk在小鼠和人骨髓细胞发育和功能中的作用。最后，这些结果可能会改变我们对XLA发病机制的理解以及治疗患者的治疗方法。

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.