Stress systems exacerbate the inflammatory response after corneal abrasion in sleep-deprived mice via the IL-17 signaling pathway

Yunxia Xue; Pengyang Xu; Yu Hu; Sijing Liu; Ruyu Yan; Shutong Liu; Yan Li; Jun Liu; Ting Fu; Zhijie Li

doi:10.1016/j.mucimm.2024.02.009

Stress systems exacerbate the inflammatory response after corneal abrasion in sleep-deprived mice via the IL-17 signaling pathway

Mucosal Immunol. 2024 Feb 28:S1933-0219(24)00018-7. doi: 10.1016/j.mucimm.2024.02.009. Online ahead of print.

Authors

Yunxia Xue¹, Pengyang Xu², Yu Hu³, Sijing Liu¹, Ruyu Yan¹, Shutong Liu³, Yan Li¹, Jun Liu¹, Ting Fu¹, Zhijie Li⁴

Affiliations

¹ International Ocular Surface Research Center, Institute of Ophthalmology and Key Laboratory for Regenerative Medicine, Jinan University Medical School, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
² International Ocular Surface Research Center, Institute of Ophthalmology and Key Laboratory for Regenerative Medicine, Jinan University Medical School, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China; Department of Pathology, Nanyang Second General Hospital, Nanyang City, Henan, China.
³ International Ocular Surface Research Center, Institute of Ophthalmology and Key Laboratory for Regenerative Medicine, Jinan University Medical School, Guangzhou, China.
⁴ International Ocular Surface Research Center, Institute of Ophthalmology and Key Laboratory for Regenerative Medicine, Jinan University Medical School, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China. Electronic address: tzhijieli@jnu.edu.cn.

PMID: 38428739
DOI: 10.1016/j.mucimm.2024.02.009

Abstract

Sleep deprivation (SD) has a wide range of adverse health effects. However, the mechanisms by which SD influences corneal pathophysiology and its post-wound healing remain unclear. This study aimed to examine the basic physiological characteristics of the cornea in mice subjected to SD and determine the pathophysiological response to injury after corneal abrasion. Using a multi-platform water environment method as an SD model, we found that SD leads to disturbances of corneal proliferative, sensory, and immune homeostasis as well as excessive inflammatory response and delayed repair after corneal abrasion by inducing hyperactivation of the sympathetic nervous system and hypothalamic-pituitary-adrenal axis. Pathophysiological changes in the cornea mainly occurred through the activation of the IL-17 signaling pathway. Blocking both adrenergic and glucocorticoid synthesis and locally neutralizing IL-17A significantly improved corneal homeostasis and the excessive inflammatory response and delay in wound repair following corneal injury in SD-treated mice. These results indicate that optimal sleep quality is essential for the physiological homeostasis of the cornea and its well-established repair process after injury. Additionally, these observations provide potential therapeutic targets to ameliorate SD-induced delays in corneal wound repair by inhibiting or blocking the activation of the stress system and its associated IL-17 signaling pathway.