Pedram Hamrah1, Ying Liu, Qiang Zhang, M Reza Dana. 1. Laboratory of Immunology, Schepens Eye Research Institute, and the Massachusetts Eye and Ear Infirmary, and the Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
Abstract
BACKGROUND: The normal corneal stroma is endowed with large numbers of resident dendritic cells (DCs). The purpose of this study was to examine the phenotype and distribution of these cells in inflammation. METHODS: Normal and inflamed murine corneas were excised at different time points and immunofluorescence staining with multiple antibodies was performed by confocal microscopy on whole-mounted corneal stromas to characterize and evaluate the distribution of DCs in inflammation. RESULTS: CD11c+CD11b+ myeloid DCs were present throughout the anterior stroma. In the periphery of the normal cornea, nearly one half were major histocompatibility complex (MHC) class II+CD80+CD86+, while they were uniformly MHC class II-CD80-CD86- in the center. In inflammation, in addition to a significant increase in the number of DCs, a majority up-regulated their expression of MHC class II, CD80, and CD86, indicating their state of maturation. The up-regulation of MHC class II and costimulatory molecules on DCs was seen as early as 24 hours after induction of inflammation or transplantation. In addition to the CD11c+DCs in the anterior stroma, a CD11c-CD11b+ population of monocytes/macrophages was present almost exclusively in the posterior stroma of the cornea. These cells were found throughout all layers of the stroma, and in increased numbers, after induction of inflammation. CONCLUSION: The present study demonstrates, for the first time, the phenotypic changes and distribution of resident stromal DCs in corneal inflammation. Clinical Relevance These novel data suggest that the cornea is capable of participating in immune and inflammatory responses by virtue of its own heterogeneous population of DCs.
BACKGROUND: The normal corneal stroma is endowed with large numbers of resident dendritic cells (DCs). The purpose of this study was to examine the phenotype and distribution of these cells in inflammation. METHODS: Normal and inflamed murine corneas were excised at different time points and immunofluorescence staining with multiple antibodies was performed by confocal microscopy on whole-mounted corneal stromas to characterize and evaluate the distribution of DCs in inflammation. RESULTS:CD11c+CD11b+ myeloid DCs were present throughout the anterior stroma. In the periphery of the normal cornea, nearly one half were major histocompatibility complex (MHC) class II+CD80+CD86+, while they were uniformly MHC class II-CD80-CD86- in the center. In inflammation, in addition to a significant increase in the number of DCs, a majority up-regulated their expression of MHC class II, CD80, and CD86, indicating their state of maturation. The up-regulation of MHC class II and costimulatory molecules on DCs was seen as early as 24 hours after induction of inflammation or transplantation. In addition to the CD11c+DCs in the anterior stroma, a CD11c-CD11b+ population of monocytes/macrophages was present almost exclusively in the posterior stroma of the cornea. These cells were found throughout all layers of the stroma, and in increased numbers, after induction of inflammation. CONCLUSION: The present study demonstrates, for the first time, the phenotypic changes and distribution of resident stromal DCs in corneal inflammation. Clinical Relevance These novel data suggest that the cornea is capable of participating in immune and inflammatory responses by virtue of its own heterogeneous population of DCs.
Authors: Tina B McKay; Yashar Seyed-Razavi; Chiara E Ghezzi; Gabriela Dieckmann; Thomas J F Nieland; Dana M Cairns; Rachel E Pollard; Pedram Hamrah; David L Kaplan Journal: Prog Retin Eye Res Date: 2018-11-16 Impact factor: 21.198