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Eosinophils promote corneal wound healing via the 12/15‐lipoxygenase pathway
Author(s) -
Ogawa Mamoru,
Ishihara Tomoaki,
Isobe Yosuke,
Kato Taiga,
Kuba Keiji,
Imai Yumiko,
Uchino Yuichi,
Tsubota Kazuo,
Arita Makoto
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202000483r
Subject(s) - wound healing , lipid signaling , eosinophil , corneal epithelium , conjunctiva , lipidomics , lipoxygenase , chemistry , inflammation , immunology , microbiology and biotechnology , epithelium , biology , medicine , pathology , biochemistry , enzyme , asthma
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 A 4 (LXA 4 ) 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.