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) 对小鼠和人类骨髓细胞功能作用的表征

• 批准号: 207627402
• 负责人: Professorin Dr. Cornelia Brunner
• 金额: --
• 依托单位: Forschungsbereich Onkologie / Tumorimmunologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2013-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/207627402?language=en
• 关键词: Characterization; Role; Bruton; Tyrosine; Kinase

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.

布鲁顿的酪氨酸激酶（BTK）的基因编码中的突变引起人类X连锁的agammagamaglobloblobolinemia（XLA），其特征是由于缺乏免疫球蛋白，因此几乎完全缺乏成熟的B细胞，因此是由于缺乏免疫抑制剂而获得了复发性细菌感染。最近的一项研究表明，XLA患者中只有26％的年龄在21岁以上。然而，BTK不仅在B细胞中表达，而在其他造血细胞中也表达，包括髓样谱系的细胞，而是BTK对XLA髓样细胞功能的影响讨论了有争议的。最近，我们显示了小鼠中BTK缺乏中性粒细胞的深刻成熟和功能缺陷。为了更多地了解BTK在髓样舱中的作用，我们建议在这里进行新的尝试和方法。使用体内实验鼠标模型取决于第一行，主要取决于髓样细胞的作用，例如实验性自身免疫性脑脊髓炎（EAE）或伤口愈合模型或人类髓样细胞，其中BTK表达或功能将下调下调节，并“人性化的小鼠”的作用，以使我们的乳液表达构成，以至于我们的表达是造成人类的表达。 BTK/BTK用于小鼠和人的髓样细胞发育和功能。最后，这些结果可能会改变我们对XLA发病机理以及治疗患者的治疗方法的理解。