bims-actimu Biomed News
on Actinopathies in inborn errors of immunity
Issue of 2024‒01‒21
one paper selected by
Elodie Busch, University of Strasbourg

  1. J Cell Sci. 2024 Jan 15. pii: jcs.261774. [Epub ahead of print]
      Neutrophil directed motility is necessary for host defense, but its dysregulation can also cause collateral tissue damage. Actinopathies are monogenic disorders that affect the actin cytoskeleton and lead to immune dysregulation. Deficiency in ARPC1B, a component of the ARP2/3 complex, results in vascular neutrophilic inflammation; however, the mechanism remains unclear. Here, we generated human iPSC-derived neutrophils that are deficient in ARPC1B that show impaired neutrophil migration and a switch from pseudopodia to the formation of elongated filopodia. We show, using a blood vessel on a chip model, that primary human neutrophils have impaired movement across an endothelium deficient in APRC1B. We also show that the combined deficiency of ARPC1B in iNeutrophils and endothelium results in further reduction in neutrophil migration. Taken together, these results suggest that ARPC1B in endothelium is sufficient to drive neutrophil behavior. Further, the findings provide support for using the iPSC system to understand human neutrophil biology and model disease in a genetically tractable system.
    Keywords:  Arp2/3; Endothelial cells; IPSC-derived neutrophils; Migration; Neutrophil; PLB-985 cells