{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T05:14:24Z","timestamp":1773724464974,"version":"3.50.1"},"reference-count":72,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T00:00:00Z","timestamp":1651017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["R01ES032553"],"award-info":[{"award-number":["R01ES032553"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["1I01BX001176"],"award-info":[{"award-number":["1I01BX001176"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006955","name":"Office of Extramural Research, National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006955","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Acute inflammatory exacerbations (AIEs) represent immune-driven deteriorations of many chronic lung conditions, including COPD, asthma, and pulmonary fibrosis (PF). The first line of therapy is represented by broad-spectrum immunomodulation. Among the several inflammatory populations mobilizing during AIEs, eosinophils have been identified as promising indicators of an active inflammatory exacerbation. To better study the eosinophil-parenchymal crosstalk during AIE-PF, this work leverages a clinically relevant model of inflammatory exacerbations triggered by inducible expression of a mutation in the alveolar epithelial type 2 cell Surfactant Protein-C gene [SP-C<jats:sup>I73T<\/jats:sup>]. Unbiased single-cell sequencing analysis of controls and SP-C<jats:sup>I73T<\/jats:sup> mutants at a time coordinated with peak eosinophilia (14\u00a0days) defined heightened inflammatory activation, chemotaxis, and survival signaling (IL-6, IL-4\/13, STAT3, Glucocorticoid Receptor, mTOR, and MYC) in eosinophils. To study the impact of eosinophils in inflammatory exacerbations, the SP-C<jats:sup>I73T<\/jats:sup> line was crossed with eosinophil lineage deficient mice (GATA1<jats:sup>\u0394dbl<\/jats:sup>) to produce the SP-C<jats:sup>I73T<\/jats:sup>GATA1<jats:sup>KO<\/jats:sup> line. Time course analysis (7\u201342\u00a0days) demonstrated improved lung histology, survival, and reduced inflammation in SP-C<jats:sup>I73T<\/jats:sup>GATA1<jats:sup>KO<\/jats:sup> cohorts. Spectral flow cytometry of tissue digests confirmed eosinophil depletion in GATA1<jats:sup>KO<\/jats:sup> mice and the absence of a compensatory shift in neutrophils and immature monocyte recruitment. Eosinophil deletion resulted in progressive monocyte-derived macrophage accumulation (14\u00a0days post-injury), combined with declines in CD3<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup> lymphocyte and B220<jats:sup>+<\/jats:sup> B cell abundance. Histochemical analysis revealed atypical inflammatory cell activation in SP-C<jats:sup>I73T<\/jats:sup>GATA1<jats:sup>KO<\/jats:sup> mice, with reduced numbers of Arg-1<jats:sup>+<\/jats:sup> and iNOS<jats:sup>+<\/jats:sup> cells, but increases in <jats:italic>tgfb1<\/jats:italic> mRNA expression in bronchoalveolar lavage cells and tissue. Dexamethasone treatment (1\u00a0mg\/kg daily, i.p.) was utilized to investigate corticosteroid efficacy in highly eosinophilic exacerbations induced by mutant SP-C<jats:sup>I73T<\/jats:sup>. Dexamethasone successfully reduced total and eosinophil (CD11b<jats:sup>+<\/jats:sup>SigF<jats:sup>+<\/jats:sup>CD11c<jats:sup>\u2212<\/jats:sup>) counts at 14\u00a0days and was linked to reduced evidence of structural damage and perivascular infiltrate. Together, these results illustrate the deleterious role of eosinophils in inflammatory events preceding lung fibrosis and demonstrate the efficacy of corticosteroid treatment in highly eosinophilic exacerbations induced by mutant SP-C<jats:sup>I73T<\/jats:sup>.<\/jats:p>","DOI":"10.3389\/fphar.2022.875887","type":"journal-article","created":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T07:45:15Z","timestamp":1651045515000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Immunophenotyping of Acute Inflammatory Exacerbations of Lung Injury Driven by Mutant Surfactant Protein-C: A Role for Inflammatory Eosinophils"],"prefix":"10.3389","volume":"13","author":[{"given":"Jacklyn","family":"Nguyen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brittnie S.","family":"Armstrong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie","family":"Cowman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaniv","family":"Tomer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shivakumar R.","family":"Veerabhadraiah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael F.","family":"Beers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Venosa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1002\/ppul.20970","article-title":"Familial Interstitial Disease with I73T Mutation: A Mid- and Long-Term Study","volume":"44","author":"Abou Taam","year":"2009","journal-title":"Pediatr. Pulmonol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"eaba1983","DOI":"10.1126\/sciadv.aba1983","article-title":"Single-Cell RNA-Seq Reveals Ectopic and Aberrant Lung-Resident Cell Populations in Idiopathic Pulmonary Fibrosis","volume":"6","author":"Adams","year":"2020","journal-title":"Sci. Adv."},{"key":"B3","doi-asserted-by":"publisher","first-page":"234.218","DOI":"10.1165\/rcmb.2020-0387OC","article-title":"Antifibrotics Modify B-Cell Induced Fibroblast Migration and Activation in IPF Patients","volume":"204","author":"Ali","year":"2020","journal-title":"J. Immunol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1038\/s41590-018-0276-y","article-title":"Reference-Based Analysis of Lung Single-Cell Sequencing Reveals a Transitional Profibrotic Macrophage","volume":"20","author":"Aran","year":"2019","journal-title":"Nat. Immunol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1186\/s12931-019-1216-6","article-title":"Aberrant Populations of Circulating T Follicular Helper Cells and Regulatory B Cells Underlying Idiopathic Pulmonary Fibrosis","volume":"20","author":"Asai","year":"2019","journal-title":"Respir. Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.1183\/13993003.01370-2015","article-title":"Blood Eosinophils as a Marker of Response to Inhaled Corticosteroids in COPD","volume":"47","author":"Barnes","year":"2016","journal-title":"Eur. Respir. J."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1111\/all.13760","article-title":"Inflammatory Endotypes in COPD","volume":"74","author":"Barnes","year":"2019","journal-title":"Allergy"},{"key":"B8","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1189\/jlb.0210108","article-title":"Innate Immune Processes Are Sufficient for Driving Silicosis in Mice","volume":"88","author":"Beamer","year":"2010","journal-title":"J. Leukoc. Biol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1111\/j.1600-0854.2011.01223.x","article-title":"A Nonaggregating Surfactant Protein C Mutant Is Misdirected to Early Endosomes and Disrupts Phospholipid Recycling","volume":"12","author":"Beers","year":"2011","journal-title":"Traffic"},{"key":"B10","doi-asserted-by":"publisher","first-page":"S6","DOI":"10.1186\/1465-9921-14-S1-S6","article-title":"Recommendations on Treatment for IPF","volume":"14","author":"Behr","year":"2013","journal-title":"Respir. Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1183\/09031936.04.00000104","article-title":"Interstitial Lung Disease in a Baby with a De Novo Mutation in the SFTPC Gene","volume":"24","author":"Brasch","year":"2004","journal-title":"Eur. Respir. J."},{"key":"B12","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.rmcr.2016.07.010","article-title":"Eosinophil Alveolitis in Two Patients with Idiopathic Pulmonary Fibrosis","volume":"19","author":"Brix","year":"2016","journal-title":"Respir. Med. Case Rep."},{"key":"B13","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/j.jpeds.2004.10.028","article-title":"A Common Mutation in the Surfactant Protein C Gene Associated with Lung Disease","volume":"146","author":"Cameron","year":"2005","journal-title":"J. Pediatr."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2775","DOI":"10.2147\/COPD.S175017","article-title":"Blood Eosinophils and Inhaled Corticosteroids in Patients with COPD: Systematic Review and Meta-Analysis","volume":"13","author":"Cheng","year":"2018","journal-title":"Int. J. Chron. Obstruct. Pulmon. Dis."},{"key":"B15","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.anai.2020.04.006","article-title":"Relative Efficacy and Safety of Inhaled Corticosteroids in Patients with Asthma: Systematic Review and Network Meta-Analysis","volume":"125","author":"Chipps","year":"2020","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1164\/rccm.201604-0801CI","article-title":"Acute Exacerbation of Idiopathic Pulmonary Fibrosis. An International Working Group Report","volume":"194","author":"Collard","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1378\/chest.09-0790","article-title":"Identification of Early Interstitial Lung Disease in an Individual with Genetic Variations in ABCA3 and SFTPC","volume":"137","author":"Crossno","year":"2010","journal-title":"Chest"},{"key":"B18","doi-asserted-by":"publisher","first-page":"139","DOI":"10.3389\/fmed.2017.00139","article-title":"Interleukin-13 in Asthma and Other Eosinophilic Disorders","volume":"4","author":"Doran","year":"2017","journal-title":"Front. Med. (Lausanne)"},{"key":"B19","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1093\/nar\/30.1.207","article-title":"Gene Expression Omnibus: NCBI Gene Expression and Hybridization Array Data Repository","volume":"30","author":"Edgar","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1186\/1465-9921-12-94","article-title":"Impaired Resolution of Inflammatory Response in the Lungs of JF1\/Msf Mice Following Carbon Nanoparticle Instillation","volume":"12","author":"Ganguly","year":"2011","journal-title":"Respir. Res."},{"key":"B21","doi-asserted-by":"publisher","first-page":"761496","DOI":"10.3389\/fphar.2021.761496","article-title":"Cell Origin and iNOS Function Are Critical to Macrophage Activation Following Acute Lung Injury","volume":"12","author":"Golden","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1038\/s41385-018-0082-8","article-title":"Characterization of CD28null T Cells in Idiopathic Pulmonary Fibrosis","volume":"12","author":"Habiel","year":"2019","journal-title":"Mucosal Immunol."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00811-2017","article-title":"Acute Exacerbations of Idiopathic Pulmonary Fibrosis: Tough to Define; Tougher to Manage","volume":"49","author":"Hambly","year":"2017","journal-title":"Eur. Respir. J."},{"key":"B24","doi-asserted-by":"publisher","first-page":"L33","DOI":"10.1152\/ajplung.00217.2014","article-title":"A Non-BRICHOS SFTPC Mutant (SP-Ci73t) Linked to Interstitial Lung Disease Promotes a Late Block in Macroautophagy Disrupting Cellular Proteostasis and Mitophagy","volume":"308","author":"Hawkins","year":"2015","journal-title":"Am. J. Physiol. Lung Cel. Mol. Physiol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1002\/jlb.65.2.187","article-title":"T Cell independence of Bleomycin-Induced Pulmonary Fibrosis","volume":"65","author":"Helene","year":"1999","journal-title":"J. Leukoc. Biol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/j.ebiom.2019.10.050","article-title":"Endotype-Phenotyping May Predict a Treatment Response in Progressive Fibrosing Interstitial Lung Disease","volume":"50","author":"Hoffmann-Vold","year":"2019","journal-title":"EBioMedicine"},{"key":"B27","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/s41598-018-36875-2","article-title":"Lipid Uptake by Alveolar Macrophages Drives Fibrotic Responses to Silica Dust","volume":"9","author":"Hou","year":"2019","journal-title":"Sci. Rep."},{"key":"B28","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/icb.2017.22","article-title":"Idiopathic Pulmonary Fibrosis and a Role for Autoimmunity","volume":"95","author":"Hoyne","year":"2017","journal-title":"Immunol. Cel. Biol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1016\/j.pt.2016.05.004","article-title":"Eosinophils in Helminth Infection: Defenders and Dupes","volume":"32","author":"Huang","year":"2016","journal-title":"Trends Parasitol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1900646","DOI":"10.1183\/13993003.00646-2019","article-title":"A Spatially Restricted Fibrotic Niche in Pulmonary Fibrosis Is Sustained by M-CSF\/M-CSFR Signalling in Monocyte-Derived Alveolar Macrophages","volume":"55","author":"Joshi","year":"2020","journal-title":"Eur. Respir. J."},{"key":"B31","doi-asserted-by":"publisher","first-page":"499","DOI":"10.3978\/j.issn.2072-1439.2015.01.17","article-title":"Acute Exacerbation of Idiopathic Pulmonary Fibrosis-A Review of Current and Novel Pharmacotherapies","volume":"7","author":"Juarez","year":"2015","journal-title":"J. Thorac. Dis."},{"key":"B32","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/s12931-016-0400-1","article-title":"Risk Factors for an Acute Exacerbation of Idiopathic Pulmonary Fibrosis","volume":"17","author":"Kakugawa","year":"2016","journal-title":"Respir. Res."},{"key":"B33","doi-asserted-by":"publisher","first-page":"e0248889","DOI":"10.1371\/journal.pone.0248889","article-title":"Lung Gene Expression and Single Cell Analyses Reveal Two Subsets of Idiopathic Pulmonary Fibrosis (IPF) Patients Associated with Different Pathogenic Mechanisms","volume":"16","author":"Karman","year":"2021","journal-title":"PLoS One"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1700761","DOI":"10.1183\/13993003.00761-2017","article-title":"Blood Eosinophil Count and Exacerbation Risk in Patients with COPD","volume":"50","author":"Kerkhof","year":"2017","journal-title":"Eur. Respir. J."},{"key":"B35","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1007\/s12016-018-8712-1","article-title":"Understanding Asthma Phenotypes, Endotypes, and Mechanisms of Disease","volume":"56","author":"Kuruvilla","year":"2019","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1093\/toxsci\/kfy309","article-title":"Role of Macrophages in Acute Lung Injury and Chronic Fibrosis Induced by Pulmonary Toxicants","volume":"168","author":"Laskin","year":"2019","journal-title":"Toxicol. Sci."},{"key":"B37","doi-asserted-by":"publisher","first-page":"176","DOI":"10.3389\/fmed.2017.00176","article-title":"Acute Exacerbation in Interstitial Lung Disease","volume":"4","author":"Leuschner","year":"2017","journal-title":"Front. Med."},{"key":"B38","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1378\/chest.92.1.7","article-title":"The Eosinophil in Idiopathic Pulmonary Fibrosis","volume":"92","author":"Libby","year":"1987","journal-title":"Chest"},{"key":"B39","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/978-1-4939-7113-8_2","article-title":"The Bleomycin Model of Pulmonary Fibrosis","volume":"1627","author":"Liu","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1159\/000475780","article-title":"Idiopathic Pulmonary Fibrosis: Molecular Endotypes of Fibrosis Stratifying Existing and Emerging Therapies","volume":"93","author":"Magnini","year":"2017","journal-title":"Respiration"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1841","DOI":"10.1001\/jama.2021.4956","article-title":"Effect of Antimicrobial Therapy on Respiratory Hospitalization or Death in Adults with Idiopathic Pulmonary Fibrosis: The CleanUP-IPF Randomized Clinical Trial","volume":"325","author":"Martinez","year":"2021","journal-title":"JAMA"},{"key":"B42","doi-asserted-by":"publisher","first-page":"L379","DOI":"10.1152\/ajplung.00010.2008","article-title":"Animal Models of Acute Lung Injury","volume":"295","author":"Matute-Bello","year":"2008","journal-title":"Am. J. Physiol. Lung Cel. Mol. Physiol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1702120","DOI":"10.1183\/13993003.02120-2017","article-title":"CSF1R Inhibition Prevents Radiation Pulmonary Fibrosis by Depletion of Interstitial Macrophages","volume":"51","author":"Meziani","year":"2018","journal-title":"Eur. Respir. J."},{"key":"B44","doi-asserted-by":"publisher","first-page":"2387","DOI":"10.1084\/jem.20162152","article-title":"Monocyte-Derived Alveolar Macrophages Drive Lung Fibrosis and Persist in the Lung over the Life Span","volume":"214","author":"Misharin","year":"2017","journal-title":"J. Exp. Med."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1549","DOI":"10.2147\/COPD.S192047","article-title":"Effects of Air Pollution on Acute Exacerbation of Chronic Obstructive Pulmonary Disease: a Descriptive Retrospective Study (Pol-AECOPD)","volume":"14","author":"Morantes-Caballero","year":"2019","journal-title":"Int. J. Chron. Obstruct Pulmon Dis."},{"key":"B46","doi-asserted-by":"publisher","first-page":"3053","DOI":"10.21873\/invivo.12601","article-title":"Silica Induced Lung Fibrosis Is Associated with Senescence, Fgr, and Recruitment of Bone Marrow Monocyte\/Macrophages","volume":"35","author":"Mukherjee","year":"2021","journal-title":"In Vivo"},{"key":"B47","doi-asserted-by":"publisher","first-page":"2220","DOI":"10.3389\/fimmu.2018.02220","article-title":"Involvement and Possible Role of Eosinophils in Asthma Exacerbation","volume":"9","author":"Nakagome","year":"2018","journal-title":"Front. Immunol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1183\/09059180.00002512","article-title":"Incidence and Prevalence of Idiopathic Pulmonary Fibrosis: Review of the Literature","volume":"21","author":"Nalysnyk","year":"2012","journal-title":"Eur. Respir. Rev."},{"key":"B49","doi-asserted-by":"publisher","first-page":"4008","DOI":"10.1172\/JCI99287","article-title":"Expression of Mutant Sftpc in Murine Alveolar Epithelia Drives Spontaneous Lung Fibrosis","volume":"128","author":"Nureki","year":"2018","journal-title":"J. Clin. Invest."},{"key":"B50","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1164\/ajrccm.185.5.587","article-title":"Steroids in Idiopathic Pulmonary Fibrosis Acute Exacerbation: Defenders or Killers?","volume":"185","author":"Papiris","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1769","DOI":"10.1177\/0271678X20943823","article-title":"The ARRIVE Guidelines 2.0: Updated Guidelines for Reporting Animal Research","volume":"40","author":"Percie Du Sert","year":"2020","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"B52","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1016\/j.ajpath.2011.04.025","article-title":"Eosinophils Contribute to IL-4 Production and Shape the T-Helper Cytokine Profile and Inflammatory Response in Pulmonary Cryptococcosis","volume":"179","author":"Piehler","year":"2011","journal-title":"Am. J. Pathol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1016\/j.celrep.2015.06.028","article-title":"Mice with Pulmonary Fibrosis Driven by Telomere Dysfunction","volume":"12","author":"Povedano","year":"2015","journal-title":"Cell Rep."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1968","DOI":"10.1056\/NEJMoa1113354","article-title":"Prednisone, Azathioprine, and N-Acetylcysteine for Pulmonary Fibrosis","volume":"366","author":"Raghu","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"B55","doi-asserted-by":"publisher","first-page":"1517","DOI":"10.1164\/rccm.201712-2410OC","article-title":"Single-Cell Transcriptomic Analysis of Human Lung Provides Insights into the Pathobiology of Pulmonary Fibrosis","volume":"199","author":"Reyfman","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B56","doi-asserted-by":"publisher","first-page":"2071","DOI":"10.1056\/NEJMoa1402584","article-title":"Efficacy and Safety of Nintedanib in Idiopathic Pulmonary Fibrosis","volume":"370","author":"Richeldi","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"B57","doi-asserted-by":"publisher","first-page":"CD002880","DOI":"10.1002\/14651858.cd002880","article-title":"Corticosteroids for Idiopathic Pulmonary Fibrosis","volume":"2003","author":"Richeldi","year":"2003","journal-title":"Cochrane Database Syst. Rev."},{"key":"B58","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1165\/rcmb.2021-0101ED","article-title":"B Cells in Idiopathic Pulmonary Fibrosis: Targeting Immune Cells with Antifibrotic Agents","volume":"64","author":"Roman","year":"2021","journal-title":"Am. J. Respir. Cel. Mol. Biol"},{"key":"B59","doi-asserted-by":"publisher","first-page":"1298","DOI":"10.1164\/rccm.201611-2263OC","article-title":"Deep Proteome Profiling Reveals Common Prevalence of MZB1-Positive Plasma B Cells in Human Lung and Skin Fibrosis","volume":"196","author":"Schiller","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B60","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/S2213-2600(18)30508-3","article-title":"Increased Monocyte Count as a Cellular Biomarker for Poor Outcomes in Fibrotic Diseases: A Retrospective, Multicentre Cohort Study","volume":"7","author":"Scott","year":"2019","journal-title":"Lancet Respir. Med."},{"key":"B61","doi-asserted-by":"publisher","first-page":"170048","DOI":"10.1183\/16000617.0048-2017","article-title":"Shared Epithelial Pathways to Lung Repair and Disease","volume":"26","author":"Spella","year":"2017","journal-title":"Eur. Respir. Rev."},{"key":"B62","doi-asserted-by":"publisher","first-page":"118","DOI":"10.3389\/fmed.2017.00118","article-title":"Exploring Animal Models that Resemble Idiopathic Pulmonary Fibrosis","volume":"4","author":"Tashiro","year":"2017","journal-title":"Front. Med. (Lausanne)"},{"key":"B63","doi-asserted-by":"publisher","first-page":"7552","DOI":"10.1073\/pnas.0701009104","article-title":"Adult-Onset Pulmonary Fibrosis Caused by Mutations in Telomerase","volume":"104","author":"Tsakiri","year":"2007","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"B64","doi-asserted-by":"publisher","first-page":"665818","DOI":"10.3389\/fimmu.2021.665818","article-title":"Role of CCR2+ Myeloid Cells in Inflammation Responses Driven by Expression of a Surfactant Protein-C Mutant in the Alveolar Epithelium","volume":"12","author":"Venosa","year":"2021","journal-title":"Front. Immunol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"2760","DOI":"10.4049\/jimmunol.1900039","article-title":"Epithelial Expression of an Interstitial Lung Disease-Associated Mutation in Surfactant Protein-C Modulates Recruitment and Activation of Key Myeloid Cell Populations in Mice","volume":"202","author":"Venosa","year":"2019","journal-title":"J. Immunol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1165\/rcmb.2015-0120OC","article-title":"Characterization of Distinct Macrophage Subpopulations During Nitrogen Mustard-Induced Lung Injury and Fibrosis","volume":"54","author":"Venosa","year":"2016","journal-title":"Am. J. Respir. Cel. Mol. Biol"},{"key":"B67","doi-asserted-by":"publisher","first-page":"L1487","DOI":"10.1152\/ajplung.00276.2015","article-title":"Protective Role of Spleen-Derived Macrophages in Lung Inflammation, Injury, and Fibrosis Induced by Nitrogen Mustard","volume":"309","author":"Venosa","year":"2015","journal-title":"Am. J. Physiol. Lung Cel. Mol. Physiol."},{"key":"B68","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1136\/thx.2005.045187","article-title":"Asthma Exacerbations. 3: Pathogenesis","volume":"61","author":"Wark","year":"2006","journal-title":"Thorax"},{"key":"B69","doi-asserted-by":"publisher","first-page":"e88947","DOI":"10.1172\/jci.insight.88947","article-title":"Epithelial-Macrophage Interactions Determine Pulmonary Fibrosis Susceptibility in Hermansky-Pudlak Syndrome","volume":"1","author":"Young","year":"2016","journal-title":"JCI Insight"},{"key":"B70","doi-asserted-by":"publisher","first-page":"1280","DOI":"10.1038\/modpathol.3880234","article-title":"Eosinophilic Pneumonia-Like Areas in Idiopathic Usual Interstitial Pneumonia","volume":"13","author":"Yousem","year":"2000","journal-title":"Mod. Pathol."},{"key":"B71","doi-asserted-by":"publisher","first-page":"2037","DOI":"10.1016\/j.jaci.2018.04.010","article-title":"Blood Eosinophil Count Thresholds and Exacerbations in Patients with Chronic Obstructive Pulmonary Disease","volume":"141","author":"Yun","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"6883","DOI":"10.1038\/s41598-018-25358-z","article-title":"mTOR Complexes Differentially Orchestrates Eosinophil Development in Allergy","volume":"8","author":"Zhu","year":"2018","journal-title":"Sci. Rep."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.875887\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T07:45:21Z","timestamp":1651045521000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.875887\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,27]]},"references-count":72,"alternative-id":["10.3389\/fphar.2022.875887"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2022.875887","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,27]]},"article-number":"875887"}}