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However, mechanistic studies in experimental asthma models have been inconclusive, identifying both protective and pathogenic effects of calprotectin. To clarify the role of calprotectin in asthma, calprotectin-deficient S100A9\u2212\/\u2212 and wild-type (WT) C57BL\/6 mice were compared in a murine model of allergic airway inflammation. Mice were intranasally challenged with extracts of the clinically relevant allergen, Alternaria alternata (Alt Ext), or PBS every third day over 9 days. On Day 10, BAL fluid and lung tissue homogenates were harvested and allergic airway inflammation was assessed. Alt Ext challenge induced release of S100A8\/S100A9 to the alveolar space and increased protein expression in the alveolar epithelium of WT mice. Compared with WT mice, S100A9\u2212\/\u2212 mice displayed significantly enhanced allergic airway inflammation, including production of IL-13, CCL11, CCL24, serum IgE, eosinophil recruitment, and airway resistance and elastance. In response to Alt Ext, S100A9\u2212\/\u2212 mice accumulated significantly more IL-13+IL-5+CD4+ T-helper type 2 cells. S100A9\u2212\/\u2212 mice also accumulated a significantly lower proportion of CD4+ T regulatory (Treg) cells in the lung that had significantly lower expression of CD25. Calprotectin enhanced WT Treg cell suppressive activity in vitro. Therefore, this study identifies a role for the innate immune protein, S100A9, in protection from CD4+ T-helper type 2 cell hyperinflammation in response to Alt Ext. This protection is mediated, at least in part, by CD4+ Treg cell function.<\/jats:p>","DOI":"10.1165\/rcmb.2018-0217oc","type":"journal-article","created":{"date-parts":[[2019,4,3]],"date-time":"2019-04-03T19:12:07Z","timestamp":1554318727000},"page":"459-468","source":"Crossref","is-referenced-by-count":38,"title":["The Innate Immune Protein S100A9 Protects from T-Helper Cell Type 2\u2013mediated Allergic Airway Inflammation"],"prefix":"10.1093","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7458-6129","authenticated-orcid":false,"given":"Lauren D.","family":"Palmer","sequence":"first","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology"},{"name":"Vanderbilt Institute for Infection, Immunology and Inflammation, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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Noel","family":"Maxwell","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and"},{"name":"Department of Chemistry, Center for Structural Biology, Vanderbilt University, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2180-0790","authenticated-orcid":false,"given":"Walter J.","family":"Chazin","sequence":"additional","affiliation":[{"name":"Vanderbilt Institute for Infection, Immunology and Inflammation, and"},{"name":"Department of Biochemistry and"},{"name":"Department of Chemistry, Center for Structural Biology, Vanderbilt University, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1429-7875","authenticated-orcid":false,"suffix":"Jr.","given":"R. 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