QIMR Berghofer

PAG1 limits allergen-induced type 2 inflammation in the murine lung.


BACKGROUND: Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1) is a transmembrane adaptor protein that affects immune-receptor signaling in T and B cells. Evidence from genome-wide association studies of asthma suggests that genetic variants that regulate the expression of PAG1 are associated with asthma risk. However, it is not known whether PAG1 expression is causally related to asthma pathophysiology. Here, we investigated the role of PAG1 in a preclinical mouse model of house dust mite (HDM)-induced allergic sensitization and allergic airway inflammation. METHODS: ) and wild-type (WT) mice were sensitized or sensitized/challenged to HDM, and hallmark features of allergic inflammation were assessed. The contribution of T cells was assessed through depletion (anti-CD4 antibody) and adoptive transfer studies. RESULTS: 2 cell differentiation was both T cell intrinsic and extrinsic. CONCLUSION: 2 differentiation. As a consequence, PAG1-deficiency predisposed towards allergic sensitization and increased the severity of experimental asthma. This article is protected by copyright. All rights reserved.

Authors Ullah, Md Ashik; Vicente, Cristina T; Collinson, Natasha; Curren, Bodie; Sikder, Md Al Amin; Sebina, Ismail; Simpson, Jennifer; Varelias, Antiopi; Lindquist, Jonathan A; Ferreira, Manuel A R; Phipps, Simon
Pages 336-345
Volume 75
Date 1/07/2019
Grant ID
Funding Body National Health and Medical Research Council of Australia
URL http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1111/all.13991