{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T23:00:55Z","timestamp":1793055655396,"version":"4.5.0"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"European Union\u2019s Seventh Framework Programme","award":["FP7\/2007-2013"],"award-info":[{"award-number":["FP7\/2007-2013"]}]},{"name":"Innovative Medicines Initiative Joint Undertaking","award":["grant 115010"],"award-info":[{"award-number":["grant 115010"]}]},{"name":"Swedish Heart Lung Foundation","award":["HLF 20180290"],"award-info":[{"award-number":["HLF 20180290"]}]},{"name":"Swedish Heart Lung Foundation","award":["HLF 20200693"],"award-info":[{"award-number":["HLF 20200693"]}]},{"name":"European Union\u2019s Seventh Framework Programme","award":["Innovative Medicines Initiative Joint Undertaking (grant 115010)"],"award-info":[{"award-number":["Innovative Medicines Initiative Joint Undertaking (grant 115010)"]}]},{"name":"Swedish Heart Lung Foundation","award":["HLF 20180290"],"award-info":[{"award-number":["HLF 20180290"]}]},{"name":"Swedish Heart Lung Foundation","award":["HLF 20200693"],"award-info":[{"award-number":["HLF 20200693"]}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Mast cells (MCs) play a role in inflammation and both innate and adaptive immunity, but their involvement in severe asthma (SA) remains undefined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We investigated the phenotypic characteristics of the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Diseases Outcomes) asthma cohort by applying published MC activation signatures to the sputum cell transcriptome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Eighty-four participants with SA, 20 with mild\/moderate asthma (MMA), and 16 healthy participants without asthma were studied. We calculated enrichment scores (ESs) for nine MC activation signatures by asthma severity, sputum granulocyte status, and three previously defined sputum molecular phenotypes or transcriptome-associated clusters (TACs) 1, 2, and 3 using gene set variation analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>MC signatures except unstimulated, repeated Fc\u03b5R1-stimulated and IFN-\u03b3\u2013stimulated signatures were enriched in SA. A Fc\u03b5R1-IgE\u2013stimulated and a single-cell signature from asthmatic bronchial biopsies were highly enriched in eosinophilic asthma and in the TAC1 molecular phenotype. Subjects with a high ES for these signatures had elevated sputum amounts of similar genes and pathways. IL-33\u2013 and LPS-stimulated MC signatures had greater ES in neutrophilic and mixed granulocytic asthma and in the TAC2 molecular phenotype. These subjects exhibited neutrophil, NF-\u03baB (nuclear factor-\u03baB), and IL-1\u03b2\/TNF-\u03b1 (tumor necrosis factor-\u03b1) pathway activation. The IFN-\u03b3\u2013stimulated signature had the greatest ES in TAC2 and TAC3 that was associated with responses to viral infection. Similar results were obtained in an independent ADEPT (Airway Disease Endotyping for Personalized Therapeutics) asthma cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Gene signatures of MC activation allow the detection of SA phenotypes and indicate that MCs can be induced to take on distinct transcriptional phenotypes associated with specific clinical phenotypes. IL-33\u2013stimulated MC signature was associated with severe neutrophilic asthma, whereas IgE-activated MC was associated with an eosinophilic phenotype.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202102-0355oc","type":"journal-article","created":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T13:27:41Z","timestamp":1637674061000},"page":"397-411","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":68,"title":["Association of Differential Mast Cell Activation with Granulocytic Inflammation in Severe Asthma"],"prefix":"10.1093","volume":"205","author":[{"given":"Angelica","family":"Tiotiu","sequence":"first","affiliation":[{"name":"National Heart and Lung Institute and"},{"name":"Department of Pulmonology, University Hospital of Nancy, Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusef","family":"Badi","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute and"},{"name":"Data Science Institute, Department of Computing, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazanin Zounemat","family":"Kermani","sequence":"additional","affiliation":[{"name":"Data Science Institute, Department of Computing, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Sanak","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Kolmert","sequence":"additional","affiliation":[{"name":"The Institute of Environmental Medicine and"},{"name":"Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden"},{"name":"Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8113-0653","authenticated-orcid":false,"given":"Craig E.","family":"Wheelock","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip M.","family":"Hansbro","sequence":"additional","affiliation":[{"name":"Centre for Inflammation, Centenary Institute, University of Technology Sydney, School of Life Sciences, Faculty of Science, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven-Erik","family":"Dahl\u00e9n","sequence":"additional","affiliation":[{"name":"The Institute of Environmental Medicine and"},{"name":"Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Sterk","sequence":"additional","affiliation":[{"name":"Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, the Netherlands; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ratko","family":"Djukanovic","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Southampton, Southampton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yike","family":"Guo","sequence":"additional","affiliation":[{"name":"Data Science Institute, Department of Computing, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Mumby","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2101-8843","authenticated-orcid":false,"given":"Ian M.","family":"Adcock","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute and"},{"name":"Data Science Institute, Department of Computing, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7101-1426","authenticated-orcid":false,"given":"Kian Fan","family":"Chung","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute and"},{"name":"Data Science Institute, Department of Computing, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,2,15]]},"reference":[{"key":"2026022020591580100_bib1","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1183\/09031936.00202013","article-title":"International ERS\/ATS guidelines on definition, evaluation and treatment of severe asthma","volume":"43","author":"Chung","year":"2014","journal-title":"Eur Respir J"},{"key":"2026022020591580100_bib2","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1111\/all.13771","article-title":"Precision medicine for the discovery of treatable mechanisms in severe asthma","volume":"74","author":"Chung","year":"2019","journal-title":"Allergy"},{"key":"2026022020591580100_bib3","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/j.chest.2016.06.009","article-title":"New developments in mast cell biology: clinical implications","volume":"150","author":"Arthur","year":"2016","journal-title":"Chest"},{"key":"2026022020591580100_bib4","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.jaci.2018.01.034","article-title":"Mast cells signal their importance in health and disease","volume":"142","author":"Olivera","year":"2018","journal-title":"J Allergy Clin Immunol"},{"key":"2026022020591580100_bib5","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1111\/cea.12675","article-title":"Mast cells in asthma\u2014state of the art","volume":"46","author":"Bradding","year":"2016","journal-title":"Clin Exp Allergy"},{"key":"2026022020591580100_bib6","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1183\/13993003.01129-2016","article-title":"Severe asthma exists despite suppressed tissue inflammation: findings of the U-BIOPRED study","volume":"48","author":"Wilson","year":"2016","journal-title":"Eur Respir J"},{"key":"2026022020591580100_bib7","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1164\/rccm.201002-0295OC","article-title":"Mast cell phenotype, location, and activation in severe asthma. Data from the severe asthma research program","volume":"183","author":"Balzar","year":"2011","journal-title":"Am J Respir Crit Care Med"},{"key":"2026022020591580100_bib8","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1183\/13993003.02135-2016","article-title":"T-helper cell type 2 (Th2) and non-Th2 molecular phenotypes of asthma using sputum transcriptomics in U-BIOPRED","volume":"49","author":"Kuo","year":"2017","journal-title":"Eur Respir J"},{"key":"2026022020591580100_bib9","doi-asserted-by":"crossref","first-page":"4241","DOI":"10.3390\/ijms20174241","article-title":"Mast cell responses to viruses and pathogen products","volume":"20","author":"Marshall","year":"2019","journal-title":"Int J Mol Sci"},{"key":"2026022020591580100_bib10","doi-asserted-by":"crossref","first-page":"F1000","DOI":"10.12688\/f1000research.22037.1","article-title":"Recent advances in mast cell activation and regulation","volume":"9","author":"Kim","year":"2020","journal-title":"F1000 Res"},{"key":"2026022020591580100_bib11","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.jaci.2015.01.014","article-title":"Innate and adaptive T cells in asthmatic patients: relationship to severity and disease mechanisms","volume":"136","author":"Hinks","year":"2015","journal-title":"J Allergy Clin Immunol"},{"key":"2026022020591580100_bib12","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cell.2019.09.009","article-title":"An allosteric anti-tryptase antibody for the treatment of mast cell-mediated severe asthma","volume":"179","author":"Maun","year":"2019","journal-title":"Cell"},{"key":"2026022020591580100_bib13","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.jaci.2021.01.033","article-title":"Sputum mast cell\/basophil gene expression relates to inflammatory and clinical features of severe asthma","volume":"148","author":"Winter","year":"2021","journal-title":"J Allergy Clin Immunol"},{"key":"2026022020591580100_bib14","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1183\/13993003.00779-2015","article-title":"Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort","volume":"46","author":"Shaw","year":"2015","journal-title":"Eur Respir J"},{"key":"2026022020591580100_bib15","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1183\/09041950.005s1693","article-title":"Lung volumes and forced ventilatory flows. Report working party standardization of lung function tests, European community for steel and coal","volume":"16","author":"Quanjer","year":"1993","journal-title":"Eur Respir J Suppl"},{"key":"2026022020591580100_bib16","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1136\/thx.52.6.498","article-title":"The use of induced sputum to investigate airway inflammation [editorial]","volume":"52","author":"Pavord","year":"1997","journal-title":"Thorax"},{"key":"2026022020591580100_bib17","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1164\/rccm.201909-1869OC","article-title":"Urinary leukotriene E4 and prostaglandin D2 metabolites increase in adult and childhood severe asthma characterized by type 2 inflammation. A clinical observational study","volume":"203","author":"Kolmert","year":"2021","journal-title":"Am J Respir Crit Care Med"},{"key":"2026022020591580100_bib18","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1093\/biostatistics\/4.2.249","article-title":"Exploration, normalization, and summaries of high density oligonucleotide array probe level data","volume":"4","author":"Irizarry","year":"2003","journal-title":"Biostatistics"},{"key":"2026022020591580100_bib19","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.jaci.2017.02.045","article-title":"Sputum transcriptomics reveal upregulation of IL-1 receptor family members in patients with severe asthma","volume":"141","author":"Rossios","year":"2018","journal-title":"J Allergy Clin Immunol"},{"key":"2026022020591580100_bib20","first-page":"6","article-title":"tranSMART: an open source and community-driven informatics and data sharing platform for clinical and translational research","volume":"2013","author":"Athey","year":"2013","journal-title":"AMIA Jt Summits Transl Sci Proc"},{"key":"2026022020591580100_bib21","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1471-2105-14-7","article-title":"GSVA: gene set variation analysis for microarray and RNA-seq data","volume":"14","author":"H\u00e4nzelmann","year":"2013","journal-title":"BMC Bioinformatics"},{"key":"2026022020591580100_bib22","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/nmeth.3337","article-title":"Robust enumeration of cell subsets from tissue expression profiles","volume":"12","author":"Newman","year":"2015","journal-title":"Nat Methods"},{"key":"2026022020591580100_bib23","doi-asserted-by":"crossref","first-page":"7837","DOI":"10.4049\/jimmunol.175.12.7837","article-title":"Identification of T cell-restricted genes, and signatures for different T cell responses, using a comprehensive collection of microarray datasets","volume":"175","author":"Chtanova","year":"2005","journal-title":"J Immunol"},{"key":"2026022020591580100_bib24","doi-asserted-by":"crossref","first-page":"3677","DOI":"10.4049\/jimmunol.0901333","article-title":"Activation of mast cells by trimeric G protein Gi3; coupling to the A3 adenosine receptor directly and upon T cell contact","volume":"184","author":"Baram","year":"2010","journal-title":"J Immunol"},{"key":"2026022020591580100_bib25","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/j.jaci.2016.01.017","article-title":"Repeated Fc\u03b5RI triggering reveals modified mast cell function related to chronic allergic responses in tissue","volume":"138","author":"Suurmond","year":"2016","journal-title":"J Allergy Clin Immunol"},{"key":"2026022020591580100_bib26","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/1471-2164-7-210","article-title":"Genome-wide gene expression profiling of human mast cells stimulated by IgE or FcepsilonRI-aggregation reveals a complex network of genes involved in inflammatory responses","volume":"7","author":"Jayapal","year":"2006","journal-title":"BMC Genomics"},{"key":"2026022020591580100_bib27","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1038\/s41591-019-0468-5","article-title":"A cellular census of human lungs identifies novel cell states in health and in asthma","volume":"25","author":"Vieira Braga","year":"2019","journal-title":"Nat Med"},{"key":"2026022020591580100_bib28","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.jaci.2015.01.036","article-title":"IL-13 mediates IL-33-dependent mast cell and type 2 innate lymphoid cell effects on bronchial epithelial cells","volume":"136","author":"Nagarkar","year":"2015","journal-title":"J Allergy Clin Immunol"},{"key":"2026022020591580100_bib29","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.1182\/blood-2002-12-3929","article-title":"Identification of specific gene expression profiles in human mast cells mediated by Toll-like receptor 4 and FcepsilonRI","volume":"102","author":"Okumura","year":"2003","journal-title":"Blood"},{"key":"2026022020591580100_bib30","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s12931-018-0968-8","article-title":"Modulation of blood inflammatory markers by benralizumab in patients with eosinophilic airway diseases","volume":"20","author":"Sridhar","year":"2019","journal-title":"Respir Res"},{"key":"2026022020591580100_bib31","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/sj.gene.6364173","article-title":"Immune response in silico (IRIS): immune-specific genes identified from a compendium of microarray expression data","volume":"6","author":"Abbas","year":"2005","journal-title":"Genes Immun"},{"key":"2026022020591580100_bib32","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1186\/s12931-016-0482-9","article-title":"Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study","volume":"17","author":"Loza","year":"2016","journal-title":"Respir Res"},{"key":"2026022020591580100_bib33","volume-title":"R: A language and environment for statistical computing.","author":"R Core Team","year":"2017"},{"key":"2026022020591580100_bib34","author":"Storey","year":"2021"},{"key":"2026022020591580100_bib35","doi-asserted-by":"crossref","DOI":"10.1007\/978-0-387-98141-3","volume-title":"ggplot2: Elegant graphics for data analysis.","author":"Wickham","year":"2009"},{"key":"2026022020591580100_bib36","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"2026022020591580100_bib37","doi-asserted-by":"crossref","first-page":"eabb7221","DOI":"10.1126\/sciimmunol.abb7221","article-title":"Human airway mast cells proliferate and acquire distinct inflammation-driven phenotypes during type 2 inflammation","volume":"6","author":"Dwyer","year":"2021","journal-title":"Sci Immunol"},{"key":"2026022020591580100_bib38","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1111\/all.14633","article-title":"Single-cell molecular profiling provides a high-resolution map of basophil and mast cell development","volume":"76","author":"Hamey","year":"2021","journal-title":"Allergy"},{"key":"2026022020591580100_bib39","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1038\/ni.3445","article-title":"Expression profiling of constitutive mast cells reveals a unique identity within the immune system","volume":"17","author":"Dwyer","year":"2016","journal-title":"Nat Immunol"},{"key":"2026022020591580100_bib40","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1111\/cea.13732","article-title":"Gene signatures from scRNA-seq accurately quantify mast cells in biopsies in asthma","volume":"50","author":"Jiang","year":"2020","journal-title":"Clin Exp Allergy"},{"key":"2026022020591580100_bib41","doi-asserted-by":"crossref","first-page":"108593","DOI":"10.1016\/j.clim.2020.108593","article-title":"Transcriptome of airway neutrophils reveals an interferon response in life-threatening respiratory syncytial virus infection","volume":"220","author":"Besteman","year":"2020","journal-title":"Clin Immunol"},{"key":"2026022020591580100_bib42","doi-asserted-by":"crossref","first-page":"e104080","DOI":"10.1371\/journal.pone.0104080","article-title":"Evaluation of genome-wide expression profiles of blood and sputum neutrophils in cystic fibrosis patients before and after antibiotic therapy","volume":"9","author":"Conese","year":"2014","journal-title":"PloS One"},{"key":"2026022020591580100_bib43","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/j.jaci.2019.01.048","article-title":"Mast cells: Promoters of health and modulators of disease","volume":"144","author":"Maurer","year":"2019","journal-title":"J Allergy Clin Immunol"},{"key":"2026022020591580100_bib44","doi-asserted-by":"crossref","first-page":"S46","DOI":"10.1016\/j.jaci.2019.01.031","article-title":"Mast cells within cellular networks","volume":"144","author":"Stassen","year":"2019","journal-title":"J Allergy Clin Immunol"},{"key":"2026022020591580100_bib45","doi-asserted-by":"crossref","first-page":"2538","DOI":"10.3390\/cells9122538","article-title":"Mast cell functions linking innate sensing to adaptive immunity","volume":"9","author":"Katsoulis-Dimitriou","year":"2020","journal-title":"Cells"},{"key":"2026022020591580100_bib46","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.immuni.2005.09.015","article-title":"IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines","volume":"23","author":"Schmitz","year":"2005","journal-title":"Immunity"},{"key":"2026022020591580100_bib47","doi-asserted-by":"crossref","first-page":"4375","DOI":"10.4049\/jimmunol.1003020","article-title":"The danger signal, extracellular ATP, is a sensor for an airborne allergen and triggers IL-33 release and innate Th2-type responses","volume":"186","author":"Kouzaki","year":"2011","journal-title":"J Immunol"},{"key":"2026022020591580100_bib48","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1038\/ni.3370","article-title":"Interleukin 33 is a guardian of barriers and a local alarmin","volume":"17","author":"Martin","year":"2016","journal-title":"Nat Immunol"},{"key":"2026022020591580100_bib49","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.cyto.2007.09.013","article-title":"Interleukin (IL)-33 induces the release of pro-inflammatory mediators by mast cells","volume":"40","author":"Moulin","year":"2007","journal-title":"Cytokine"},{"key":"2026022020591580100_bib50","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1016\/j.jaci.2020.01.036","article-title":"Mast cells initiate the vascular response to contact allergens by sensing cell stress","volume":"145","author":"Hoppe","year":"2020","journal-title":"J Allergy Clin Immunol"},{"key":"2026022020591580100_bib51","article-title":"Mapping atopic dermatitis and anti-IL-22 response signatures to type 2-low severe neutrophilic asthma","volume-title":"J Allergy Clin Immunol","author":"Badi","year":"2021"},{"key":"2026022020591580100_bib52","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1111\/cea.12077","article-title":"Levels of prostaglandin E(2) and Cysteinyl-leukotrienes in sputum supernatant of patients with asthma: the effect of smoking","volume":"43","author":"Kontogianni","year":"2013","journal-title":"Clin Exp Allergy"},{"key":"2026022020591580100_bib53","doi-asserted-by":"crossref","first-page":"4219","DOI":"10.1038\/s41598-017-03674-0","article-title":"Interleukin 33 exacerbates antigen driven airway hyperresponsiveness, inflammation and remodeling in a mouse model of asthma","volume":"7","author":"Sj\u00f6berg","year":"2017","journal-title":"Sci Rep"},{"key":"2026022020591580100_bib54","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/j.jaci.2021.03.044","article-title":"Astegolimab (anti-ST2) efficacy and safety in adults with severe asthma: a randomized clinical trial","volume":"148","author":"Kelsen","year":"2021","journal-title":"J Allergy Clin Immunol"},{"key":"2026022020591580100_bib55","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1002\/iub.555","article-title":"Signaling through Toll-like receptor 4 and mast cell-dependent innate immunity responses","volume":"63","author":"Avila","year":"2011","journal-title":"IUBMB Life"},{"key":"2026022020591580100_bib56","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.jaci.2020.04.018","article-title":"Sputum microbiome profiles identify severe asthma phenotypes of relative stability at 12 to 18 months","volume":"147","author":"Abdel-Aziz","year":"2021","journal-title":"J Allergy Clin Immunol"},{"key":"2026022020591580100_bib57","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1182\/blood-2005-06-2271","article-title":"FcepsilonR1 and toll-like receptors mediate synergistic signals to markedly augment production of inflammatory cytokines in murine mast cells","volume":"107","author":"Qiao","year":"2006","journal-title":"Blood"},{"key":"2026022020591580100_bib58","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.bbrc.2009.11.082","article-title":"Synergistic augmentation of inflammatory cytokine productions from murine mast cells by monomeric IgE and toll-like receptor ligands","volume":"391","author":"Takenaka","year":"2010","journal-title":"Biochem Biophys Res Commun"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/205\/4\/397\/67008868\/ajrccm_205_4_397.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/205\/4\/397\/67008868\/ajrccm_205_4_397.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T01:59:33Z","timestamp":1771639173000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/205\/4\/397\/8492067"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2]]},"references-count":58,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,2,15]]},"published-print":{"date-parts":[[2022,2,15]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.202102-0355oc","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,2]]},"published":{"date-parts":[[2022,2]]},"assertion":[{"value":"2021-02-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}