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Publication : Scaffolding protein Gab1 regulates myeloid dendritic cell migration in allergic asthma.

First Author  Zhang Y Year  2016
Journal  Cell Res Volume  26
Issue  11 Pages  1226-1241
PubMed ID  27811945 Mgi Jnum  J:273991
Mgi Id  MGI:6295210 Doi  10.1038/cr.2016.124
Citation  Zhang Y, et al. (2016) Scaffolding protein Gab1 regulates myeloid dendritic cell migration in allergic asthma. Cell Res 26(11):1226-1241
abstractText  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.
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