Eosinophils promote corneal wound healing via the 12/15‐lipoxygenase pathway

• Published in: The FASEB journal Vol. 34; no. 9; pp. 12492 - 12501
• Main Authors: Ogawa, Mamoru, Ishihara, Tomoaki, Isobe, Yosuke, Kato, Taiga, Kuba, Keiji, Imai, Yumiko, Uchino, Yuichi, Tsubota, Kazuo, Arita, Makoto
• Format: Journal Article
• Language: English
• Published: United States 01-09-2020
• Subjects: alox15; Animals; Arachidonate 12-Lipoxygenase - physiology; Arachidonate 15-Lipoxygenase - physiology; Cornea - pathology; Corneal Injuries - pathology; corneal wound healing; eosinophils; Eosinophils - cytology; Eosinophils - enzymology; lipid mediator; lipoxygenase; metabolomics; Mice; Mice, Inbred C57BL; Mice, Knockout; Wound Healing; corneal wound healing; lipoxygenase; eosinophils; alox15; metabolomics; lipid mediator
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.202000483R

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.