Eosinophils promote corneal wound healing via the 12/15‐lipoxygenase pathway. Issue 9 (28th July 2020)

• Record Type: Journal Article
• Authors: Ogawa, Mamoru; Ishihara, Tomoaki; Isobe, Yosuke; Kato, Taiga; Kuba, Keiji; Imai, Yumiko; Uchino, Yuichi; Tsubota, Kazuo; Arita, Makoto
• Is Part Of: FASEB journal. Volume 34:Issue 9(2020)
• Page Start: 12492
• Page End: 12501
• Publication Date: 2020-07-28
• Subjects: alox15 -- corneal wound healing -- eosinophils -- lipid mediator -- lipoxygenase -- metabolomics; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.202000483R
• Languages: English
• ISSNs: 0892-6638

Abstract

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.