{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T13:53:01Z","timestamp":1791813181133,"version":"4.3.4"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2012,3,1]],"date-time":"2012-03-01T00:00:00Z","timestamp":1330560000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The fungal allergen, Alternaria, is specifically associated with severe asthma, including life-threatening exacerbations. To better understand the acute innate airway response to Alternaria, naive wild-type (WT) mice were challenged once intranasally with Alternaria. Naive WT mice developed significant bronchoalveolar lavage eosinophilia following Alternaria challenge when analyzed 24 h later. In contrast to Alternaria, neither Aspergillus nor Candida induced bronchoalveolar lavage eosinophilia. Gene microarray analysis of airway epithelial cell brushings demonstrated that Alternaria-challenged naive WT mice had a &amp;gt;20-fold increase in the level of expression of found in inflammatory zone 1 (FIZZ1\/Retnla), a resistin-like molecule. Lung immunostaining confirmed strong airway epithelial FIZZ1 expression as early as 3 h after a single Alternaria challenge that persisted for \u22655 d and was significantly reduced in STAT6-deficient, but not protease-activated receptor 2-deficient mice. Bone marrow chimera studies revealed that STAT6 expressed in lung cells was required for epithelial FIZZ1 expression, whereas STAT6 present in bone marrow-derived cells contributed to airway eosinophilia. Studies investigating which cells in the nonchallenged lung bind FIZZ1 demonstrated that CD45+CD11c+ cells (macrophages and dendritic cells), as well as collagen-1\u2013producing CD45\u2212 cells (fibroblasts), can bind to FIZZ1. Importantly, direct administration of recombinant FIZZ1 to naive WT mice led to airway eosinophilia, peribronchial fibrosis, and increased thickness of the airway epithelium. Thus, Alternaria induces STAT6\u2013dependent acute airway eosinophilia and epithelial FIZZ1 expression that promotes airway fibrosis and epithelial thickness. This may provide some insight into the uniquely pathogenic aspects of Alternaria-associated asthma.<\/jats:p>","DOI":"10.4049\/jimmunol.1101632","type":"journal-article","created":{"date-parts":[[2012,2,11]],"date-time":"2012-02-11T14:33:25Z","timestamp":1328970805000},"page":"2622-2629","source":"Crossref","is-referenced-by-count":85,"title":["<i>Alternaria<\/i>\n                    Induces STAT6-Dependent Acute Airway Eosinophilia and Epithelial FIZZ1 Expression That Promotes Airway Fibrosis and Epithelial Thickness"],"prefix":"10.1093","volume":"188","author":[{"given":"Taylor A","family":"Doherty","sequence":"first","affiliation":[{"name":"Department of Medicine, University of California San Diego , La Jolla, CA 92093"},{"name":"Division of Immune Regulation, La Jolla Institute for Allergy and Immunology , La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naseem","family":"Khorram","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego , La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kotaro","family":"Sugimoto","sequence":"additional","affiliation":[{"name":"Department of Medicine, Lung Biology Center, University of California San Francisco , San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean","family":"Sheppard","sequence":"additional","affiliation":[{"name":"Department of Medicine, Lung Biology Center, University of California San Francisco , San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Rosenthal","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego , La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Youn","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego , La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexa","family":"Pham","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego , La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego , La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Croft","sequence":"additional","affiliation":[{"name":"Division of Immune Regulation, La Jolla Institute for Allergy and Immunology , La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H","family":"Broide","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego , La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,3,15]]},"reference":[{"key":"2025032409591459700_r1","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1183\/09031936.00138707","article-title":"Global strategy for asthma management and prevention: GINA executive summary","volume":"31","author":"Bateman","year":"2008","journal-title":"Eur. 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