@article{8ef9f74c70fa49bab23b839f78f3b1c1,
title = "Eosinophils promote corneal wound healing via the 12/15-lipoxygenase pathway",
abstract = "Lipid mediators play important roles in regulating inflammatory responses and tissue homeostasis. Since 12/15-lipoxygenase (12/15-LOX)-derived lipid mediators such as lipoxin A4 (LXA4) and protectin D1 (PD1) protect against corneal epithelial cell damage, the major cell types that express 12/15-LOX and contribute to the corneal wound healing process are of particular interest. Here, we found that eosinophils were the major cell type expressing 12/15-LOX during the corneal wound healing process. Eosinophils were recruited into the conjunctiva after corneal epithelium wounding, and eosinophil-deficient and/or eosinophil-specific 12/15-LOX knockout mice showed delayed corneal wound healing compared with wild-type mice. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based mediator lipidomics revealed that a series of 12/15-LOX-derived mediators were significantly decreased in eosinophil-deficient mice and topical application of 17-hydroxydocosahexaenoic acid (17-HDoHE), a major 12/15-LOX-derived product, restored the phenotype. These results indicate that 12/15-LOX-expressing eosinophils, by locally producing pro-resolving mediators, significantly contribute to the corneal wound healing process in the eye.",
keywords = "alox15, corneal wound healing, eosinophils, lipid mediator, lipoxygenase, metabolomics",
author = "Mamoru Ogawa and Tomoaki Ishihara and Yosuke Isobe and Taiga Kato and Keiji Kuba and Yumiko Imai and Yuichi Uchino and Kazuo Tsubota and Makoto Arita",
note = "Funding Information: This study was supported by the Japan Society for the Promotion of Science (KAKENHI JP15H05897, 15H05898, and 20H00495 to MA), Program for the Advancement of Research in Core Projects in the Longevity Initiative at Keio University Global Research Institute from Keio University (MA), RIKEN Junior Research Associate Program, and Keio University Doctorate Student Grant‐In‐Aid Program (MO). The authors wish to thank Dr James J. Lee for sharing the EoCRE mice maintained in his colony. The authors wish to thank Dr Satoshi Iwamoto (Juntendo University) for assistance with corneal wound healing model. The authors also wish to thank Dr Tetsuya Kawakita (Keio University School of Medicine) for constructive comments on this research. Funding Information: This study was supported by the Japan Society for the Promotion of Science (KAKENHI JP15H05897, 15H05898, and 20H00495 to MA), Program for the Advancement of Research in Core Projects in the Longevity Initiative at Keio University Global Research Institute from Keio University (MA), RIKEN Junior Research Associate Program, and Keio University Doctorate Student Grant-In-Aid Program (MO). The authors wish to thank Dr James J. Lee for sharing the EoCRE mice maintained in his colony. The authors wish to thank Dr Satoshi Iwamoto (Juntendo University) for assistance with corneal wound healing model. The authors also wish to thank Dr Tetsuya Kawakita (Keio University School of Medicine) for constructive comments on this research. Publisher Copyright: {\textcopyright} 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology",
year = "2020",
month = sep,
day = "1",
doi = "10.1096/fj.202000483R",
language = "English",
volume = "34",
pages = "12492--12501",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "9",
}