Volume 26, No 11, Nov 2016

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 26 Issue 11, November 2016: 1226-1241

ORIGINAL ARTICLES

Scaffolding protein Gab1 regulates myeloid dendritic cell migration in allergic asthma

Yun Zhang¹, Yun Xu¹, Shuwan Liu¹, Xiaohong Guo¹, Dong Cen¹, Jiaqi Xu¹, Heyuan Li¹, Kaijun Li², Chunlai Zeng², Linrong Lu³, Yiting Zhou⁴, Huahao Shen⁵, Hongqiang Cheng^1,6, Xue Zhang^1,6 and Yuehai Ke^1,6

¹Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, China
²Lishui Central Hospital, Affiliated Lishui Hospital of Zhejiang University, Lishui, Zhejiang 323000, China
³The Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
⁴Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
⁵Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
⁶Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang 310003, China Correspondence: Yuehai Ke, Tel: +86-0571-88208713; Fax: +86-0571-88208583 E-mail: yke@zju.edu.cn

Asthma is a common allergic disorder involving a complex interplay among multiple genetic and environmental factors. Recent studies identified genetic variants of human GAB1 as a novel asthma susceptibility factor. However, the functions of Gab1 in lung remain largely unexplored. In this study, we first observed an elevation of Gab1 level in peripheral blood mononuclear cells from asthmatic patients during acute exacerbation compared with convalescence. Mice with a selectively disrupted Gab1 in myeloid dendritic cells (mDCs) considerably attenuated allergic inflammation in experimental models of asthma. Further investigations revealed a prominent reduction in CCL19-mediated migration of Gab1-deficient mDCs to draining lymph nodes and subsequent impairment of Th2-driven adaptive activation. Mechanistically, Gab1 is an essential component of the CCL19/CCR7 chemokine axis that regulates mDC migration during asthmatic responses. Together, these findings provide the first evidence for the roles of Gab1 in lung, giving us deeper understanding of asthmatic pathogenesis.

10.1038/cr.2016.124

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