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We showed that fluoxetine treatment of murine or human mast cells reduced IgE-mediated degranulation, cytokine production, and inflammatory lipid secretion, as well as signaling mediated by the mast cell activator ATP. In a mouse model of systemic anaphylaxis, fluoxetine reduced hypothermia and cytokine production. Fluoxetine was also effective in a model of allergic airway inflammation, where it reduced bronchial responsiveness and inflammation. These data show that fluoxetine suppresses mast cell activation by impeding an Fc\u025bRI-ATP positive feedback loop and support the potential repurposing of this SSRI for use in allergic disease.<\/jats:p>","DOI":"10.1126\/scisignal.abc9089","type":"journal-article","created":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T17:58:11Z","timestamp":1694541491000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":4,"title":["Fluoxetine restrains allergic inflammation by targeting an Fc\u025bRI-ATP positive feedback loop in mast cells"],"prefix":"10.1126","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4436-9558","authenticated-orcid":true,"given":"Tamara T.","family":"Haque","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7965-4335","authenticated-orcid":true,"given":"Marcela T.","family":"Taruselli","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1254-4828","authenticated-orcid":true,"given":"Sydney A.","family":"Kee","sequence":"additional","affiliation":[{"name":"Department of Biology, Virginia Commonwealth University, Richmond, VA 23284, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan M.","family":"Dailey","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2300-7902","authenticated-orcid":true,"given":"Neha","family":"Pondicherry","sequence":"additional","affiliation":[{"name":"Department of Biology, Virginia Commonwealth University, Richmond, VA 23284, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula A.","family":"Gajewski-Kurdziel","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Charles E.\u00a0Schmidt College of Medicine, Florida Atlantic University, Jupiter, FL 33458, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew P.","family":"Zellner","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5698-3400","authenticated-orcid":true,"given":"Daniel J.","family":"Stephenson","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Virginia\u2013School of Medicine, Charlottesville, VA 22903, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. 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