生物
细胞生物学
蛋白质酪氨酸磷酸酶
运动性
效应器
趋化性
磷酸酶
PI3K/AKT/mTOR通路
趋化因子
信号转导
吞噬作用
免疫学
炎症
受体
生物化学
磷酸化
作者
Morgan Giese,David A. Bennin,Taylor J. Schoen,Ashley N. Peterson,Jonathan H Schrope,Josh Brand,Ho Sun Jung,Nancy P. Keller,David J. Beebe,Huy Q. Dinh,Igor I. Slukvin,Anna Huttenlocher
标识
DOI:10.1093/jleuko/qiae039
摘要
Neutrophils are rapidly recruited to sites of infection and are critical for pathogen clearance. Therapeutic use of primary neutrophils has been limited as they have a short lifespan and are not amenable to genetic manipulation. Human induced pluripotent stem cells (iPSCs) can provide a robust source of neutrophils for infusion and are genetically tractable. However, current work has indicated that dampened intracellular signaling limits iPSC-derived neutrophil (iNeutrophil) cellular activation and antimicrobial response. Here, we show that protein tyrosine phosphatase 1B (PTP1B) inhibits intracellular signaling and dampens iNeutrophil effector function. Deletion of the PTP1B phosphatase increased PI3K and ERK signaling and was associated with increased F-actin polymerization, cell migration and phagocytosis. In contrast, other effector functions like NETosis and ROS production were reduced. PTP1B-deficient neutrophils were more responsive to A. fumigatus and displayed rapid recruitment and control of hyphal growth. Accordingly, depletion of PTP1B increased production of inflammatory factors including the neutrophil chemokine IL-8. Taken together, these findings suggest that PTP1B limits iNeutrophil motility and antimicrobial function.
科研通智能强力驱动
Strongly Powered by AbleSci AI