Weber Alexander N R, Bittner Zsofia, Liu Xiao, Dang Truong-Minh, Radsak Markus Philipp, Brunner Cornelia
Department of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, Tübingen, Germany.
Department of Internal Medicine III, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
Front Immunol. 2017 Nov 8;8:1454. doi: 10.3389/fimmu.2017.01454. eCollection 2017.
Bruton's tyrosine kinase (BTK) was initially discovered as a critical mediator of B cell receptor signaling in the development and functioning of adaptive immunity. Growing evidence also suggests multiple roles for BTK in mononuclear cells of the innate immune system, especially in dendritic cells and macrophages. For example, BTK has been shown to function in Toll-like receptor-mediated recognition of infectious agents, cellular maturation and recruitment processes, and Fc receptor signaling. Most recently, BTK was additionally identified as a direct regulator of a key innate inflammatory machinery, the NLRP3 inflammasome. BTK has thus attracted interest not only for gaining a more thorough basic understanding of the human innate immune system but also as a target to therapeutically modulate innate immunity. We here review the latest developments on the role of BTK in mononuclear innate immune cells in mouse versus man, with specific emphasis on the sensing of infectious agents and the induction of inflammation. Therapeutic implications for modulating innate immunity and critical open questions are also discussed.
布鲁顿酪氨酸激酶（BTK）最初被发现是适应性免疫发育和功能中B细胞受体信号传导的关键介质。越来越多的证据还表明，BTK在固有免疫系统的单核细胞中具有多种作用，尤其是在树突状细胞和巨噬细胞中。例如，BTK已被证明在Toll样受体介导的病原体识别、细胞成熟和募集过程以及Fc受体信号传导中发挥作用。最近，BTK还被确定为关键固有炎症机制NLRP3炎性小体的直接调节因子。因此，BTK不仅因其能更深入地从基础层面了解人类固有免疫系统而受到关注，还因其作为调节固有免疫的治疗靶点而备受瞩目。我们在此回顾了BTK在小鼠与人的单核固有免疫细胞中作用的最新进展，特别强调了病原体感知和炎症诱导。还讨论了调节固有免疫的治疗意义以及关键的未解决问题。
