CCR2\u2212 and CCR2+ corneal macrophages exhibit distinct characteristics and balance inflammatory responses after epithelial abrasion

J Liu,T Fu,F Song,J Chen,D Dong,Y Xue,Z Li,C Xiao,C Lin,Z Wang,H Pan,D Cai,Y Li,H Wang

doi:10.1038/mi.2016.139

Abstract

Macrophages are distributed throughout the body and are crucial for the restoration of damaged tissues. However, their characteristics in the cornea and roles in the repair of corneal injures are unclear. Here we show that corneal macrophages can be classified as CCR2− macrophages, which already exist in the cornea at embryonic day 12.5 (E12.5) and are similar to yolk sac-derived macrophages, microglia, in phenotype and gene expression, and CCR2+ macrophages, which do not appear in the cornea until E17.5. At a steady state, CCR2− corneal macrophages have local proliferation capacity and are rarely affected by monocytes; however, following corneal epithelial abrasion, most CCR2− corneal macrophages are replaced by monocytes. In contrast, CCR2+ macrophages are repopulated by monocytes under both a steady-state condition and following corneal wounding. Depletion of CCR2+ macrophages decreases corneal inflammation after epithelial abrasion, whereas depletion of CCR2− macrophages increases inflammation of the injured cornea. Loss of either cell type results in a delay in corneal healing. These data indicate that there are two unique macrophage populations present in the cornea, both of which participate in corneal wound healing by balancing the inflammatory response.

Highlights

Clear vision depends on an accurate refractive device
Corneal macrophage identity was confirmed using the highly specific macrophage marker, CD64.27 Using wholemount immunostaining of the cornea, we found that a large number of F4/80 þ cells were distributed throughout the cornea, and some of the F4/80 þ cells were CD64 þ (Figure 1a)
The results indicated that the phenotype of CCR2 À macrophages (F4/80 þ CD11b þ CX3CR1 þ / À CD206 þ CD301 À MHC-II À Ly6C À ) was similar to that of microglia (F4/80 þ CD11b þ CX3CR1 þ CD206 þ CD301 À MHC-II À Ly6C À ), whereas CCR2 þ macrophages (F4/80 þ CD11b þ CX3CR1 À CD206 À CD301 À MHC-II þ Ly6C þ / À )

Summary

Introduction

Clear vision depends on an accurate refractive device. The cornea, located at the anterior segment of the eye, is responsible for light refraction and transmission. Corneal integrity is maintained by a variety of cells, and their imbalance can result in serious eye diseases. Research on cells involved in maintaining corneal integrity is of the utmost importance. Recent research has highlighted the roles of immune cells in the repair of injured tissues.[1,2,3,4,5,6,7,8] Of these immune cells, macrophages appear to be concerned

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Conclusion