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CCR5 chemokine receptor mediates recruitment of MHC class II-positive Langerhans cells in the mouse corneal epithelium.

Abstract：

PURPOSE:To characterize the chemokines and chemokine receptors that mediate the effect of proinflammatory cytokines, interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha, on the recruitment of MHC class II(+) Langerhans cells (LCs) in the corneal epithelium. METHODS:A standard model for corneal LC recruitment, application of cautery to the central corneal surface was used, and the differential gene expression levels of a panel of chemokines and chemokine receptors were determined by RNase protection assay. Chemokine receptor-knockout mice were used to evaluate the recruitment of MHC class II(+) LCs to the corneal epithelium. To determine the sensitivity of selected chemokines to IL-1 and TNF-alpha stimulation, the chemokine gene expression pattern was analyzed after blockade of IL-1 and TNF receptors. RESULTS:CCR1, -2, and -5 were overexpressed in corneas after cauterization. Topical administration of soluble TNF receptor I and IL-1 receptor antagonist, which abrogated corneal LC recruitment, significantly suppressed the gene transcription levels of the ligands of CCR1 and/or -5, regulated on activation normal T-cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta. The recruitment of major histocompatibility complex (MHC) class II(+) LC was significantly suppressed in CCR5(-/-) mice and blockade of RANTES and MIP-1beta, but not in CCR1(-/-), CCR2(-/-)/MIP-1alpha(-/-), or MIP-1alpha(-/-) mice. The evaluation of epithelial CD11c(+) LC cells by confocal microscopy revealed coexpression for CCR5 primarily among B7(-) (CD80(-)/CD86(-)) subsets of these LCs but not among the mature B7(+) subsets of CD11c(+) LCs. CONCLUSIONS:These data suggest that CCR5 plays a critical role in mediating recruitment and mobilization of MHC class II(+) LCs into the corneal epithelium. Targeting CCR5 and its ligands may be a new strategy for modulating immunity.

journal_name

Invest Ophthalmol Vis Sci

journal_title

Investigative ophthalmology & visual science

authors

Yamagami S,Hamrah P,Miyamoto K,Miyazaki D,Dekaris I,Dawson T,Lu B,Gerard C,Dana MR

doi

10.1167/iovs.04-0658

keywords:

subject

Has Abstract

pub_date

2005-04-01 00:00:00

pages

1201-7

issue

eissn

0146-0404

issn

1552-5783

pii

46/4/1201

journal_volume

pub_type

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CCR5 chemokine receptor mediates recruitment of MHC class II-positive Langerhans cells in the mouse corneal epithelium.