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

• Published in: Clinical immunology (Orlando, Fla.) Vol. 179; pp. 17 - 24
• Main Authors: Suzuki, Chinatsu, Nakamura, Akihiro, Miura, Noriko, Fukai, Kunityoshi, Ohno, Naohito, Yahata, Tomoyo, Okamoto-Hamaoka, Akiko, Fujii, Maiko, Yoshioka, Ayako, Kuchitsu, Yuki, Ikeda, Kazuyuki, Hamaoka, Kenji
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2017
• Subjects: Allergy and Immunology; Animals; Aorta - metabolism; Candida albicans; Chemokine CXCL10 - blood; Chemokine CXCL9 - blood; Coronary Vessels - metabolism; Disease Models, Animal; Focal Adhesion Kinase 2 - genetics; IP-10; Kawasaki disease; Macrophages - metabolism; Mice, Knockout; Mucocutaneous Lymph Node Syndrome - blood; Mucocutaneous Lymph Node Syndrome - metabolism; Pyk2; STAT3 Transcription Factor - metabolism; Tenascin - metabolism; Vasculitis; V asculitis; Kawasaki disease; IP-10; Pyk2; Vasculitis
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2017.01.013

Abstract 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 vasc u litis. 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)