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Tropomycin receptor kinase A (TrkA) is the high-affinity receptor for nerve growth factor. AAI is associated with increased expression of TrkA by eosinophils; however, the functional role of TrkA in regulating eosinophil recruitment and contributing to AAI is poorly understood. This study identifies, to our knowledge, a novel mechanism of eotaxin-mediated activation of TrkA and its role in regulating eosinophil recruitment by using a chemical-genetic approach to specifically inhibit TrkA kinase activity with 1-NM-PP1 in TrkAF592A\u2013knock-in (TrkA-KI) eosinophils. Blockade of TrkA by 1-NM-PP1 enhanced eosinophil spreading on VCAM-1 but inhibited eotaxin-1 (CCL11)\u2013mediated eosinophil migration, calcium flux, cell polarization, and ERK1\/2 activation, suggesting that TrkA is an important player in the signaling pathway activated by eotaxin-1 during eosinophil migration. Further, blockade of matrix metalloprotease with BB-94 inhibited eotaxin-1\u2013induced TrkA activation and eosinophil migration, additively with 1-NM-PP1, indicating a role for matrix metalloproteases in TrkA activation. TrkA inhibition in Alternaria alternata\u2013challenged TrkA-KI mice markedly inhibited eosinophilia and attenuated various features of AAI. These findings are indicative of a distinctive eotaxin-mediated TrkA-dependent signaling pathway, which, in addition to other TrkA-activating mediators, contributes to eosinophil recruitment during AAI and suggests that targeting the TrkA signaling pathway to inhibit eosinophil recruitment may serve as a therapeutic strategy for management of eosinophilic inflammation in allergic airway disease, including asthma.<\/jats:p>","DOI":"10.4049\/jimmunol.1900786","type":"journal-article","created":{"date-parts":[[2019,12,23]],"date-time":"2019-12-23T23:05:16Z","timestamp":1577142316000},"page":"682-693","source":"Crossref","is-referenced-by-count":10,"title":["Regulation of Eosinophil Recruitment and Allergic Airway Inflammation by Tropomyosin Receptor Kinase A"],"prefix":"10.1093","volume":"204","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2284-0492","authenticated-orcid":false,"given":"Mythili","family":"Dileepan","sequence":"first","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota , St. Paul, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao Na","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota , St. Paul, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Idil","family":"Bastan","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota , St. Paul, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yana G","family":"Greenberg","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota , St. Paul, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6002-6868","authenticated-orcid":false,"given":"Yuying","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota , St. Paul, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9082-1029","authenticated-orcid":false,"given":"P","family":"Sriramarao","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota , St. Paul, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9763-199X","authenticated-orcid":false,"given":"Savita P","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota , St. Paul, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,2,1]]},"reference":[{"key":"2025030417510591600_r1","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/978-3-642-45106-5_5","volume-title":"Neurotrophic Factors.","author":"Deinhardt","year":"2014"},{"key":"2025030417510591600_r2","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/bs.ircmb.2014.10.002","article-title":"Biogenesis and function of the NGF\/TrkA signaling endosome","volume":"314","author":"Marlin","year":"2015","journal-title":"Int. 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