HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Chinnery, H. R. Articles by McMenamin, P. G. Search for Related Content PubMed PubMed Citation Articles by Chinnery, H. R. Articles by McMenamin, P. G.

The Chemokine Receptor CX₃CR1 Mediates Homing of MHC class II-Positive Cells to the Normal Mouse Corneal Epithelium

¹From the School of Anatomy and Human Biology and ²Red’s Spinal Cord Research Laboratory, The University of Western Australia, Crawley, Perth, Western Australia; the ³Department of Ophthalmology and Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio; and the ⁴Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.

PURPOSE. Recent investigations have revealed that populations of macrophages and dendritic cells (DCs) are present in the stroma and epithelium of the cornea, although the precise phenotype and distribution are still controversial. CX₃CR1, the sole receptor for the chemokine fractalkine, is expressed by these monocyte-derived cells. Transgenic CX₃CR1^GFP mice, in which either one (heterozygous) or both (homozygous) copies of the CX₃CR1 gene were replaced by enhanced green fluorescent protein (eGFP), were used to characterize monocyte-derived cells in the mouse cornea and to determine whether the expression of this receptor influences the recruitment of these cells into the normal cornea.

METHODS. Wholemount corneas were immunostained with anti-leukocyte antibodies to the phenotypic markers major histocompatibility complex (MHC) class II, CD169, CD68, CD11b, and CD45 and analyzed by epifluorescence and confocal microscopy. The density of intraepithelial MHC class II⁺ cells was quantified in wild-type, CX₃CR1^+/GFP heterozygous, CX₃CR1^GFP/GFP homozygous, and CX₃CR1-knockout mice.

RESULTS. There was a significant reduction in the number of MHC class II⁺ cells (putative DCs) in the corneal epithelium of CX₃CR1-deficient mice (P < 0.009) compared with wild-type mice, and the few cells that were present did not possess classic dendriform morphology. No GFP⁺ MHC class II^– cells were noted in the epithelium. Dual immunostaining of corneas in both heterozygous and homozygous (CX₃CR1-deficient) mice revealed GFP⁺ cells with a more pleomorphic morphology throughout the entire corneal stroma that were CD11b⁺ CD169⁺, and had variable degrees of expression of CD68 andMHC class II. The immunophenotype and morphology of these intrastromal cells is strongly indicative of a macrophage phenotype.

CONCLUSIONS. This study has identified a role for CX₃CR1 in the normal recruitment of MHC class II⁺ putative DCs into the corneal epithelium and establishes a model for investigating monocyte-derived cells and fractalkine/CX₃CR1 interactions during corneal disease.

This article has been cited by other articles:

				N. Eter, D. R. Engel, L. Meyer, H.-M. Helb, F. Roth, J. Maurer, F. G. Holz, and C. Kurts In Vivo Visualization of Dendritic Cells, Macrophages, and Microglial Cells Responding to Laser-Induced Damage in the Fundus of the Eye Invest. Ophthalmol. Vis. Sci., August 1, 2008; 49(8): 3649 - 3658. [Abstract] [Full Text] [PDF]

				A. B. Tarabishy, B. Aldabagh, Y. Sun, Y. Imamura, P. K. Mukherjee, J. H. Lass, M. A. Ghannoum, and E. Pearlman MyD88 Regulation of Fusarium Keratitis Is Dependent on TLR4 and IL-1R1 but Not TLR2 J. Immunol., July 1, 2008; 181(1): 593 - 600. [Abstract] [Full Text] [PDF]

				H. R. Chinnery, E. Pearlman, and P. G. McMenamin Cutting Edge: Membrane Nanotubes In Vivo: A Feature of MHC Class II+ Cells in the Mouse Cornea J. Immunol., May 1, 2008; 180(9): 5779 - 5783. [Abstract] [Full Text] [PDF]

				J. Kezic, H. Xu, H. R. Chinnery, C. C. Murphy, and P. G. McMenamin Retinal Microglia and Uveal Tract Dendritic Cells and Macrophages Are Not CX3CR1 Dependent in Their Recruitment and Distribution in the Young Mouse Eye Invest. Ophthalmol. Vis. Sci., April 1, 2008; 49(4): 1599 - 1608. [Abstract] [Full Text] [PDF]