Non-receptor type, proline-rich protein tyrosine kinase 2 (Pyk2) is a possible therapeutic target for Kawasaki disease

Publication date: Available online 3 February 2017
Source:Clinical Immunology
Author(s): Chinatsu Suzuki, Akihiro Nakamura, Noriko Miura, Kunityoshi Fukai, Naohito Ohno, Tomoyo Yahata, Akiko Okamoto-Hamaoka, Maiko Fujii, Ayako Yoshioka, Yuki Kuchitsu, Kazuyuki Ikeda, Kenji Hamaoka
Kawasaki disease (KD) is a paediatric vasculitis whose pathogenesis remains unclear. Based on experimental studies using a mouse model for KD, we report here that proline-rich protein tyrosine kinase 2 (Pyk2) plays a critical role in the onset of KD-like murine vasculitis.The mouse model for KD was prepared by administrating a Candida albicans water-soluble fraction (CAWS). Unlike CAWS-treated WT mice, CAWS-treated Pyk2-Knockout (Pyk2-KO) mice did not develop apparent vasculitis. A sustained increase in MIG/CXCL9 and IP-10/CXCL10, both of which have potent "angiostatic" activity, was observed in CAWS-treated Pyk2-KO mice. CAWS-induced activation of STAT3, which negatively regulates the expression of these chemokines, was also attenuated in macrophages derived from Pyk2-KO mice.The present study suggests that defects in Pyk2 suppress KD-like experimental vasculitis, presumably through CXCL9- and CXCL10-dependent interference with neo-angiogenesis. Since Pyk2-KO mice show no life-threatening phenotype, Pyk2 may be a promising therapeutic target for KD.(147/150 words)



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