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We previously reported dysregulated fatty acid metabolism in peripheral blood\u2010derived eosinophils from patients with severe asthma. However, functional characteristics of eosinophils present in allergic inflammatory tissues remain largely uncharacterized.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We established a method for isolating\n CD<\/jats:styled-content>\n 69\n hi<\/jats:sup>\n CCR<\/jats:styled-content>\n 3\n low<\/jats:sup>\n CXCR<\/jats:styled-content>\n 4\n \u2010<\/jats:sup>\n siglec\u20108\n int<\/jats:sup>\n eosinophils from nasal polyps of patients with eosinophilic rhinosinusitis (\n NP<\/jats:styled-content>\n \u2010\n EOS<\/jats:styled-content>\n ). Multi\u2010omics analysis including lipidomics, proteomics, and transcriptomics was performed to analyze\n NP<\/jats:styled-content>\n \u2010\n EOS<\/jats:styled-content>\n as compared to peripheral blood\u2010derived eosinophils from healthy subjects (\n PB<\/jats:styled-content>\n \u2010\n EOS<\/jats:styled-content>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Lipidomic analysis revealed impaired synthesis of prostaglandins and 15\u2010lipoxygenase (15\u2010\n LOX<\/jats:styled-content>\n )\u2010derived mediators, and selective upregulation of leukotriene D\n 4<\/jats:sub>\n production. Furthermore, proteomics and transcriptomics revealed changes in the expression of specific enzymes (\n GGT<\/jats:styled-content>\n 5,\n DPEP<\/jats:styled-content>\n 2, and 15\u2010\n LOX<\/jats:styled-content>\n ) responsible for dysregulated lipid metabolism. Ingenuity pathway analysis indicated the importance of type 2 cytokines and pattern recognition receptor pathways. Stimulation of\n PB<\/jats:styled-content>\n \u2010\n EOS<\/jats:styled-content>\n with eosinophil activators\n IL<\/jats:styled-content>\n \u20105,\n GM<\/jats:styled-content>\n \u2010\n CSF<\/jats:styled-content>\n , and agonists of\n TLR<\/jats:styled-content>\n 2 and\n NOD<\/jats:styled-content>\n 2 mimicked the observed changes in lipid metabolism.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Inflammatory tissue\u2010derived eosinophils possess a specific phenotype with dysregulated fatty acid metabolism that may be targeted therapeutically to control eosinophilic inflammatory diseases.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/all.13726","type":"journal-article","created":{"date-parts":[[2019,1,23]],"date-time":"2019-01-23T19:18:20Z","timestamp":1548271100000},"page":"1113-1124","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["Dysregulated fatty acid metabolism in nasal polyp\u2010derived eosinophils from patients with chronic rhinosinusitis"],"prefix":"10.1111","volume":"74","author":[{"given":"Jun","family":"Miyata","sequence":"first","affiliation":[{"name":"Laboratory for Metabolomics RIKEN Center for Integrative Medical Sciences Kanagawa Japan"},{"name":"Graduate School of Medical Life Science Yokohama City University Kanagawa Japan"},{"name":"Division of Pulmonary Medicine Department of Medicine Keio University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Fukunaga","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine Department of Medicine Keio University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Kawashima","sequence":"additional","affiliation":[{"name":"Laboratory for Integrative Genomics RIKEN Center for Integrative Medical Sciences Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Laboratory for Integrative Genomics RIKEN Center for Integrative Medical Sciences Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akina","family":"Saitoh","sequence":"additional","affiliation":[{"name":"Tsukuba Research Institute Ono Pharmaceutical Co., Ltd. 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Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasutomo","family":"Araki","sequence":"additional","affiliation":[{"name":"Nose Clinic Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Kikawada","sequence":"additional","affiliation":[{"name":"Nose Clinic Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Betsuyaku","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine Department of Medicine Keio University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Ohara","sequence":"additional","affiliation":[{"name":"Laboratory for Integrative Genomics RIKEN Center for Integrative Medical Sciences Yokohama 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