{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T02:55:32Z","timestamp":1785552932128,"version":"3.56.0"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,10,23]],"date-time":"2019-10-23T00:00:00Z","timestamp":1571788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Phosphoprotein associated with glycosphingolipid\u2010enriched microdomains 1 (PAG1) is a transmembrane adaptor protein that affects immune receptor signaling in T and B cells. Evidence from genome\u2010wide 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)\u2010induced allergic sensitization and allergic airway inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:italic>Pag1<\/jats:italic>\u2010deficient (<jats:italic>Pag1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>) and wild\u2010type (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\u2010CD4 antibody) and adoptive transfer studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Type 2 inflammation (eosinophilia, eotaxin\u20102 expression, IL\u20104\/IL\u20105\/IL\u201013 production, mucus production) in the airways and lungs was significantly increased in HDM sensitized\/challenged <jats:italic>Pag1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice compared to WT mice. The predisposition to allergic sensitization was associated with increased airway epithelial high\u2010mobility group box 1 (HMGB1) translocation and release, increased type 2 innate lymphoid cells (ILC2s) and monocyte\u2010derived dendritic cell numbers in the mediastinal lymph nodes, and increased T\u2010helper type 2 (T<jats:sub>H<\/jats:sub>2)\u2010cell differentiation. CD4<jats:sup>+<\/jats:sup> T\u2010cell depletion studies or the adoptive transfer of WT OVA\u2010specific CD4<jats:sup>+<\/jats:sup> T cells to WT or <jats:italic>Pag1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> recipients demonstrated that the heightened propensity for T<jats:sub>H<\/jats:sub>2\u2010cell differentiation was both T cell intrinsic and extrinsic.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>PAG1 deficiency increased airway epithelial activation, ILC2 expansion, and T<jats:sub>H<\/jats:sub>2 differentiation. As a consequence, PAG1 deficiency predisposed toward allergic sensitization and increased the severity of experimental asthma.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.13991","type":"journal-article","created":{"date-parts":[[2019,7,19]],"date-time":"2019-07-19T05:19:25Z","timestamp":1563513565000},"page":"336-345","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["PAG1 limits allergen\u2010induced type 2 inflammation in the murine lung"],"prefix":"10.1111","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0025-1796","authenticated-orcid":false,"given":"Md Ashik","family":"Ullah","sequence":"first","affiliation":[{"name":"QIMR Berghofer Medical Research Institute Brisbane Qld Australia"},{"name":"Faculty of Medicine University of Queensland Brisbane Qld Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina T.","family":"Vicente","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute Brisbane Qld Australia"},{"name":"Faculty of Medicine University of Queensland Brisbane Qld Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Collinson","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute Brisbane Qld Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bodie","family":"Curren","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute Brisbane Qld Australia"},{"name":"Faculty of Medicine University of Queensland Brisbane Qld Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Al Amin","family":"Sikder","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute Brisbane Qld Australia"},{"name":"Faculty of Medicine University of Queensland Brisbane Qld Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismail","family":"Sebina","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute Brisbane Qld Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Simpson","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute Brisbane Qld Australia"},{"name":"Faculty of Medicine University of Queensland Brisbane Qld Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antiopi","family":"Varelias","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute Brisbane Qld Australia"},{"name":"Faculty of Medicine University of Queensland Brisbane Qld Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan A.","family":"Lindquist","sequence":"additional","affiliation":[{"name":"Clinic for Nephrology and Hypertension, Diabetology and Endocrinology Otto\u2010von\u2010Guericke University Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel A. 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