Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI.
Center for Cutaneous Biology and Immunology, Department of Dermatology and Immunology Program, Henry Ford Cancer Institute, Henry Ford Health System, Detroit, MI; and.
J Immunol. 2021 Dec 1;207(11):2868-2877. doi: 10.4049/jimmunol.2001246. Epub 2021 Oct 22.
The IL-36 cytokines are known to play various roles in mediating the immune response to infection in a tissue- and pathogen-dependent manner. The present study seeks to investigate the role of IL-36R signaling in C57BL/6 mouse corneas in response to infection. IL-36α, IL-36γ, and IL-36R mice had significantly more severe keratitis than wild-type mice. At six hours postinfection, IL-36α pretreatment augmented -induced expression of IL-1Ra, IL-36γ, LCN2, and S100A8/A9. At one day postinfection, exogenous IL-36α suppressed, whereas IL-36α deficiency promoted, the expression of IL-1β. At three days postinfection, exogenous IL-36α suppressed Th1 but promoted Th2 immune response. IL-36α stimulated the infiltration of IL-22-expressing immune cells, and IL-22 neutralization resulted in more severe keratitis. IL-36α alone stimulated dendritic cell infiltration in B6 mouse corneas. Taken together, our study suggests that IL-36R signaling plays a protective role in the pathogenesis of keratitis by promoting the innate immune defense, Th2, and/or Th22/IL-22 immune responses. Exogenous IL-36α might be a potential therapy for improving the outcome of keratitis.
IL-36 细胞因子已知以组织和病原体依赖的方式在调节感染的免疫反应中发挥各种作用。本研究旨在探讨 IL-36R 信号在 C57BL/6 小鼠角膜对 感染的反应中的作用。与野生型小鼠相比，IL-36α、IL-36γ 和 IL-36R 小鼠的角膜炎更严重。感染后 6 小时，IL-36α 预处理增强了诱导的 IL-1Ra、IL-36γ、LCN2 和 S100A8/A9 的表达。感染后 1 天，外源性 IL-36α 抑制，而 IL-36α 缺乏促进 IL-1β 的表达。感染后 3 天，外源性 IL-36α 抑制 Th1 但促进 Th2 免疫反应。IL-36α 刺激表达 IL-22 的免疫细胞浸润，而 IL-22 中和导致更严重的角膜炎。IL-36α 单独刺激 B6 小鼠角膜树突状细胞的浸润。总之，我们的研究表明，IL-36R 信号通过促进先天免疫防御、Th2 和/或 Th22/IL-22 免疫反应在 角膜炎发病机制中发挥保护作用。外源性 IL-36α 可能是改善 角膜炎结局的潜在治疗方法。
