Department of Ophthalmology, University of California, San Francisco, CA 94158, USA.
UCSF Parnassus Flow Cytometry Core Facility, University of California, San Francisco, CA 94143, USA.
Int J Mol Sci. 2022 Feb 25;23(5):2574. doi: 10.3390/ijms23052574.
Mononuclear phagocytes (MP) have central importance in innate immunity, inflammation, and fibrosis. Recruited MPs, such as macrophages, are plastic cells and can switch from an inflammatory to a restorative phenotype during the healing process. However, the role of the MPs in corneal wound healing is not completely understood. The purpose of this study is to characterize the kinetics of recruited MPs and evaluate the role of macrophage metalloelastase (MMP12) in the healing process, using an in vivo corneal chemical injury model. Unwounded and wounded corneas of wild-type (WT) and mice were collected at 1, 3, and 6 days after chemical injury and processed for flow cytometry analysis. Corneal MP phenotype significantly changed over time with recruited Ly6C (proinflammatory) cells being most abundant at 1 day post-injury. Ly6C cells were highly expressed at 3 days post-injury and Ly6C (patrolling) cells became the predominant cell type at 6 days post-injury. CD11c dendritic cells were abundant in corneas from mice at 6 days post-injury. These findings show the temporal phenotypic plasticity of recruited MPs and provide valuable insight into the role of the MPs in the corneal repair response, which may help guide the future development of MP-targeted therapies.
单核吞噬细胞 (MP) 在先天免疫、炎症和纤维化中具有核心重要性。募集的 MPs,如巨噬细胞,是具有可塑性的细胞,在愈合过程中可以从炎症表型转变为修复表型。然而,MP 在角膜伤口愈合中的作用尚不完全清楚。本研究旨在使用体内角膜化学损伤模型,描述募集的 MPs 的动力学,并评估巨噬细胞金属弹性蛋白酶 (MMP12) 在愈合过程中的作用。在化学损伤后 1、3 和 6 天收集未受伤和受伤的 WT 和 小鼠的角膜,并进行流式细胞术分析。角膜 MP 表型随时间显著变化,受伤后 1 天募集的 Ly6C(促炎)细胞最为丰富。受伤后 3 天 Ly6C 细胞高表达,受伤后 6 天 Ly6C(巡逻)细胞成为主要细胞类型。受伤后 6 天, 小鼠的角膜中富含 CD11c 树突状细胞。这些发现表明募集的 MPs 的时间表型可塑性,并为 MPs 在角膜修复反应中的作用提供了有价值的见解,这可能有助于指导未来针对 MPs 的治疗方法的发展。