The chemokine receptor CX3CR1 mediates homing of MHC class II-positive cells to the normal mouse corneal epithelium

Chinnery, Holly R., Ruitenberg, Marc J., Plant, Giles W., Pearlman, Eric, Jung, Steffen and McMenamin, Paul G. (2007) The chemokine receptor CX3CR1 mediates homing of MHC class II-positive cells to the normal mouse corneal epithelium. Investigative Ophthalmology and Visual Science, 48 4: 1568-1574. doi:10.1167/iovs.06-0746

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Author Chinnery, Holly R.
Ruitenberg, Marc J.
Plant, Giles W.
Pearlman, Eric
Jung, Steffen
McMenamin, Paul G.
Title The chemokine receptor CX3CR1 mediates homing of MHC class II-positive cells to the normal mouse corneal epithelium
Journal name Investigative Ophthalmology and Visual Science   Check publisher's open access policy
ISSN 0146-0404
0146-0404
Publication date 2007-04-01
Sub-type Article (original research)
DOI 10.1167/iovs.06-0746
Open Access Status File (Publisher version)
Volume 48
Issue 4
Start page 1568
End page 1574
Total pages 7
Place of publication Rockville, M.D., U.S.A.
Publisher Association for Research in Vision and Ophthalmology
Language eng
Subject 1113 Ophthalmology and Optometry
Formatted abstract
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 CX3CR1GFP 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, CX3CR1GFP/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.
© 2007 by The Association for Research in Vision and Ophthalmology
Keyword Macrophages
Chemokine
Cornea
Dendritic cells (DCs)
Epithelium
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 47 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 21 Jan 2010, 19:58:35 EST by Gerald Martin on behalf of Faculty Of Health Sciences