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Characterization of Recruited Mononuclear Phagocytes following Corneal Chemical Injury
Authors:Ricardo Lamy  Marie Wolf  Claudia Bispo  Selene M Clay  Siyu Zheng  Finn Wolfreys  Peipei Pan  Matilda F Chan
Affiliation:1.Department of Ophthalmology, University of California, San Francisco, CA 94158, USA; (R.L.); (M.W.); (S.M.C.); (S.Z.); (F.W.); (P.P.);2.UCSF Parnassus Flow Cytometry Core Facility, University of California, San Francisco, CA 94143, USA;3.Francis I. Proctor Foundation, University of California, San Francisco, CA 94158, USA
Abstract: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 Mmp12−/− 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 Ly6Chigh (proinflammatory) cells being most abundant at 1 day post-injury. Ly6Cint cells were highly expressed at 3 days post-injury and Ly6Cneg (patrolling) cells became the predominant cell type at 6 days post-injury. CD11c+ dendritic cells were abundant in corneas from Mmp12−/− 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.
Keywords:myeloid cells  mononuclear phagocytes  monocytes  macrophages  dendritic cells  corneal injury  MMP12
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