Scaffolding protein Gab1 regulates myeloid dendritic cell migration in allergic asthma.
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.
Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, China.
Yun
Y
Zhang
Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, China.
Yun
Y
Xu
Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, China.
Shuwan
S
Liu
Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, China.
Xiaohong
X
Guo
Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, China.
Dong
D
Cen
Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, China.
Jiaqi
J
Xu
Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, China.
Heyuan
H
Li
Lishui Central Hospital, Affiliated Lishui Hospital of Zhejiang University, Lishui, Zhejiang 323000, China.
Kaijun
K
Li
Lishui Central Hospital, Affiliated Lishui Hospital of Zhejiang University, Lishui, Zhejiang 323000, China.
Chunlai
C
Zeng
The Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
Linrong
L
Lu
Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
Yiting
Y
Zhou
Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
Huahao
H
Shen
Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang 310003, China.
Hongqiang
H
Cheng
Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang 310003, China.
Xue
X
Zhang
Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang 310003, China.
Yuehai
Y
Ke
D000208:Acute Disease; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001249:Asthma / Q000378:metabolism / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D039521:CD11c Antigen / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002465:Cell Movement; D054415:Chemokine CCL19 / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D007378:Interleukins / Q000032:analysis; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D018418:Th2 Cells / Q000166:cytology / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D039521:CD11c Antigen; D054415:Chemokine CCL19; C490897:Gab1 protein, mouse; D007378:Interleukins; D010750:Phosphoproteins