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ORMDL3 promotes eosinophil trafficking and activation via regulation of integrins and CD48

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...

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Autores principales: Ha, Sung Gil, Ge, Xiao Na, Bahaie, Nooshin S., Kang, Bit Na, Rao, Amrita, Rao, Savita P., Sriramarao, P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3940275/
https://www.ncbi.nlm.nih.gov/pubmed/24056518
http://dx.doi.org/10.1038/ncomms3479
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author Ha, Sung Gil
Ge, Xiao Na
Bahaie, Nooshin S.
Kang, Bit Na
Rao, Amrita
Rao, Savita P.
Sriramarao, P.
author_facet Ha, Sung Gil
Ge, Xiao Na
Bahaie, Nooshin S.
Kang, Bit Na
Rao, Amrita
Rao, Savita P.
Sriramarao, P.
author_sort Ha, Sung Gil
collection PubMed
description 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 IL-3 and eotaxin-1. Over-expression of ORMDL3 in eosinophils causes increased rolling, distinct cytoskeletal rearrangement, ERK (1/2) phosphorylation and nuclear translocation of NF-κB. Knock-down 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. Additionally, ORMDL3 regulates IL-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.
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spelling pubmed-39402752014-03-03 ORMDL3 promotes eosinophil trafficking and activation via regulation of integrins and CD48 Ha, Sung Gil Ge, Xiao Na Bahaie, Nooshin S. Kang, Bit Na Rao, Amrita Rao, Savita P. Sriramarao, P. Nat Commun Article 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 IL-3 and eotaxin-1. Over-expression of ORMDL3 in eosinophils causes increased rolling, distinct cytoskeletal rearrangement, ERK (1/2) phosphorylation and nuclear translocation of NF-κB. Knock-down 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. Additionally, ORMDL3 regulates IL-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. 2013 /pmc/articles/PMC3940275/ /pubmed/24056518 http://dx.doi.org/10.1038/ncomms3479 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Ha, Sung Gil
Ge, Xiao Na
Bahaie, Nooshin S.
Kang, Bit Na
Rao, Amrita
Rao, Savita P.
Sriramarao, P.
ORMDL3 promotes eosinophil trafficking and activation via regulation of integrins and CD48
title ORMDL3 promotes eosinophil trafficking and activation via regulation of integrins and CD48
title_full ORMDL3 promotes eosinophil trafficking and activation via regulation of integrins and CD48
title_fullStr ORMDL3 promotes eosinophil trafficking and activation via regulation of integrins and CD48
title_full_unstemmed ORMDL3 promotes eosinophil trafficking and activation via regulation of integrins and CD48
title_short ORMDL3 promotes eosinophil trafficking and activation via regulation of integrins and CD48
title_sort ormdl3 promotes eosinophil trafficking and activation via regulation of integrins and cd48
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3940275/
https://www.ncbi.nlm.nih.gov/pubmed/24056518
http://dx.doi.org/10.1038/ncomms3479
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