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 and Kenji Kabashima ()
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Sachiko Ono: Kyoto University Graduate School of Medicine
Gyohei Egawa: Kyoto University Graduate School of Medicine
Takashi Nomura: Kyoto University Graduate School of Medicine
Akihiko Kitoh: Kyoto University Graduate School of Medicine
Teruki Dainichi: Kyoto University Graduate School of Medicine
Atsushi Otsuka: Kyoto University Graduate School of Medicine
Saeko Nakajima: Kyoto University Graduate School of Medicine
Masayuki Amagai: Keio University Graduate School of Medicine
Fumi Matsumoto: Mitsubishi Tanabe Pharma Corporation
Mami Yamamoto: Mitsubishi Tanabe Pharma Corporation
Yoshiaki Kubota: Keio University School of Medicine
Toshiyuki Takai: Tohoku University
Tetsuya Honda: Kyoto University Graduate School of Medicine
Kenji Kabashima: Kyoto University Graduate School of Medicine

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: 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.

Date: 2019
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12232-3

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DOI: 10.1038/s41467-019-12232-3

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