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

Sachiko Ono, Gyohei Egawa, Takashi Nomura, Akihiko Kitoh, Teruki Dainichi, Atsushi Otsuka, Saeko Nakajima, Masayuki Amagai, Fumi Matsumoto, Mami Yamamoto, Yoshiaki Kubota, Toshiyuki Takai, Tetsuya Honda, Kenji Kabashima

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number4432
JournalNature communications
Volume10
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Fingerprint Dive into the research topics of 'Abl family tyrosine kinases govern IgG extravasation in the skin in a murine pemphigus model'. Together they form a unique fingerprint.

  • Cite this

    Ono, S., Egawa, G., Nomura, T., Kitoh, A., Dainichi, T., Otsuka, A., Nakajima, S., Amagai, M., Matsumoto, F., Yamamoto, M., Kubota, Y., Takai, T., Honda, T., & Kabashima, K. (2019). Abl family tyrosine kinases govern IgG extravasation in the skin in a murine pemphigus model. Nature communications, 10(1), [4432]. https://doi.org/10.1038/s41467-019-12232-3