{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:20:52Z","timestamp":1760239252580,"version":"build-2065373602"},"reference-count":66,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2020,10,11]],"date-time":"2020-10-11T00:00:00Z","timestamp":1602374400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["IRTG 1911 A1","IRTG 1911 A2"],"award-info":[{"award-number":["IRTG 1911 A1","IRTG 1911 A2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Allergic asthma is a chronical pulmonary disease with high prevalence. It manifests as a maladaptive immune response to common airborne allergens and is characterized by airway hyperresponsiveness, eosinophilia, type 2 cytokine-associated inflammation, and mucus overproduction. Alveolar macrophages (AMs), although contributing to lung homeostasis and tolerance to allergens at steady state, have attracted less attention compared to professional antigen-presenting and adaptive immune cells in their contributions. Using an acute model of house dust mite-driven allergic asthma in mice, we showed that a fraction of resident tissue-associated AMs, while polarizing to the alternatively activated M2 phenotype, exhibited signs of polynucleation and polyploidy. Mechanistically, in vitro assays showed that only Granulocyte-Macrophage Colony Stimulating Factor and interleukins IL-13 and IL-33, but not IL-4 or IL-5, participate in the establishment of this phenotype, which resulted from division defects and not cell-cell fusion as shown by microscopy. Intriguingly, mRNA analysis of AMs isolated from allergic asthmatic lungs failed to show changes in the expression of genes involved in DNA damage control except for MafB. Altogether, our data support the idea that upon allergic inflammation, AMs undergo DNA damage-induced stresses, which may provide new unconventional therapeutical approaches to treat allergic asthma.<\/jats:p>","DOI":"10.3390\/ijms21207487","type":"journal-article","created":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T21:48:38Z","timestamp":1602625718000},"page":"7487","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["GM-CSF and IL-33 Orchestrate Polynucleation and Polyploidy of Resident Murine Alveolar Macrophages in a Murine Model of Allergic Asthma"],"prefix":"10.3390","volume":"21","author":[{"given":"Katharina","family":"Quell","sequence":"first","affiliation":[{"name":"Institute for Systemic Inflammation Research, University of L\u00fcbeck, 23538 L\u00fcbeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuheli","family":"Dutta","sequence":"additional","affiliation":[{"name":"Institute for Systemic Inflammation Research, University of L\u00fcbeck, 23538 L\u00fcbeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00dclk\u00fc","family":"Korkmaz","sequence":"additional","affiliation":[{"name":"Institute for Systemic Inflammation Research, University of L\u00fcbeck, 23538 L\u00fcbeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2974-433X","authenticated-orcid":false,"given":"Larissa","family":"Nogueira de Almeida","sequence":"additional","affiliation":[{"name":"Institute for Systemic Inflammation Research, University of L\u00fcbeck, 23538 L\u00fcbeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tillman","family":"Vollbrandt","sequence":"additional","affiliation":[{"name":"Cell Analysis Core Facility, University of L\u00fcbeck, 23538 L\u00fcbeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"K\u00f6nig","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, University of L\u00fcbeck, 23538 L\u00fcbeck, Germany"},{"name":"Airway Research Center North, Member of the German Center for Lung Research (DZL), 23538 L\u00fcbeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian","family":"Lewkowich","sequence":"additional","affiliation":[{"name":"Division of Immunobiology, Cincinnati Children\u2019s Hospital, Cincinnati, OH 45229, USA"},{"name":"Department of Pediatrics, University of Cincinnati, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Deepe","sequence":"additional","affiliation":[{"name":"College of Medicine, University of Cincinnati, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Admar","family":"Verschoor","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Microbiology, University of L\u00fcbeck, 23538 L\u00fcbeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1121-3178","authenticated-orcid":false,"given":"J\u00f6rg","family":"K\u00f6hl","sequence":"additional","affiliation":[{"name":"Institute for Systemic Inflammation Research, University of L\u00fcbeck, 23538 L\u00fcbeck, Germany"},{"name":"Airway Research Center North, Member of the German Center for Lung Research (DZL), 23538 L\u00fcbeck, Germany"},{"name":"Division of Immunobiology, Cincinnati Children\u2019s Hospital, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yves","family":"Laumonnier","sequence":"additional","affiliation":[{"name":"Institute for Systemic Inflammation Research, University of L\u00fcbeck, 23538 L\u00fcbeck, Germany"},{"name":"Airway Research Center North, Member of the German Center for Lung Research (DZL), 23538 L\u00fcbeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"859","DOI":"10.12998\/wjcc.v2.i12.859","article-title":"Role of immunotherapy in the treatment of allergic asthma","volume":"2","author":"Yukselen","year":"2014","journal-title":"World J. 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