Abl family tyrosine kinases govern IgG extravasation in the skin in a murine pemphigus model

Nat Commun. 2019 Sep 30;10(1):4432. doi: 10.1038/s41467-019-12232-3.


The pathway of homeostatic IgG extravasation is not fully understood, in spite of its importance for the maintenance of host immunity, the management of autoantibody-mediated disorders, and the use of antibody-based biologics. Here we show in a murine model of pemphigus, a prototypic cutaneous autoantibody-mediated disorder, that blood-circulating IgG extravasates into the skin in a time- and dose-dependent manner under homeostatic conditions. This IgG extravasation is unaffected by depletion of Fcγ receptors, but is largely attenuated by specific ablation of dynamin-dependent endocytic vesicle formation in blood endothelial cells (BECs). Among dynamin-dependent endocytic vesicles, IgG co-localizes well with caveolae in cultured BECs. An Abl family tyrosine kinase inhibitor imatinib, which reduces caveolae-mediated endocytosis, impairs IgG extravasation in the skin and attenuates the murine pemphigus manifestations. Our study highlights the kinetics of IgG extravasation in vivo, which might be a clue to understand the pathological mechanism of autoantibody-mediated autoimmune disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / metabolism
  • Autoimmune Diseases / metabolism
  • Caveolae
  • Disease Models, Animal
  • Dynamins / metabolism
  • Ear / pathology
  • Endocytosis
  • Endothelial Cells / metabolism
  • Female
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology*
  • Kinetics
  • Mice
  • Mice, Inbred C57BL
  • Pemphigus / immunology*
  • Pemphigus / metabolism*
  • Pemphigus / pathology
  • Protein-Tyrosine Kinases / metabolism*
  • Skin / immunology*
  • Skin / pathology
  • Transport Vesicles / metabolism


  • Autoantibodies
  • Immunoglobulin G
  • Protein-Tyrosine Kinases
  • Dynamins