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• W2002988594 abstract "ORM (yeast)-like protein isoform 3 (ORMDL3) has recently been identified as a candidate gene for susceptibility to asthma; however, the mechanisms by which it contributes to asthma pathogenesis are not well understood. Here we demonstrate a functional role for ORMDL3 in eosinophils in the context of allergic inflammation. Eosinophils recruited to the airways of allergen-challenged mice express ORMDL3. ORMDL3 expression in bone marrow eosinophils is localized in the endoplasmic reticulum and is induced by interleukin-3 and eotaxin-1. Overexpression of ORMDL3 in eosinophils causes increased rolling, distinct cytoskeletal rearrangement, extracellular signal-regulated kinase (1/2) phosphorylation and nuclear translocation of nuclear factor kappa B. Knockdown of ORMDL3 significantly inhibits activation-induced cell shape changes, adhesion and recruitment to sites of inflammation in vivo, combined with reduced expression of CD49d and CD18. In addition, ORMDL3 regulates interleukin-3-induced expression of CD48 and CD48-mediated eosinophil degranulation. These studies show that ORMDL3 regulates eosinophil trafficking, recruitment and degranulation, further elucidating a role for this molecule in allergic asthma and potentially other eosinophilic disorders. ORMDL3has been identified as a gene associated with asthma susceptibility, but its exact role in the pathogenesis of this disease is not well known. Here, the authors propose that induction of ORMDL3 in eosinophils modulates the expression of integrins, which could contribute to a key inflammatory event in asthma." @default.
• W2002988594 created "2016-06-24" @default.
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• W2002988594 date "2013-09-23" @default.
• W2002988594 modified "2023-10-15" @default.
• W2002988594 title "ORMDL3 promotes eosinophil trafficking and activation via regulation of integrins and CD48" @default.
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• W2002988594 doi "https://doi.org/10.1038/ncomms3479" @default.
• W2002988594 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3940275" @default.
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