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Maria J Lopez, Arsia Jamali, Deshea L Harris, Pedram Hamrah; The Chemokine Receptor CXCR4 Mediates Recruitment of CD11c+ Dendritic Cells into the Inflammed Murine Corneas.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4039.
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The naïve cornea is endowed with distinct populations of antigen-presenting cells (APCs), whose number increases significantly during inflammation. This recruitment of APCs to the cornea during inflammation is mediated, in part, by chemokine receptors as part of the multistep adhesion cascade. The purpose of this study is to identify the chemokine pathways involved in the recruitment of conventional dendritic cells (cDCs) to the cornea during inflammation.
A murine corneal suture model for inflammation was used. Wild-type (WT) BALB/c mice received 3 interrupted stromal sutures (nylon 11-0). Seven days later, 20 millions cDCs labeled with a green fluorescent marker (CFDA) were adoptively transferred intravenously (IV) via tail vein injection. These cDCs were harvested from spleens of mice that received subcutaneous FLT3-expressing melanoma cells. 30 minutes before adoptive transfer of cDCs, WT BALB/c were blocked with 50 mg/mL IV of neutralizing monoclonal antibody (MAb) against CXCR4. Twenty-four hours after adoptive transfer of labeled cDCs into host mice (8 days after suture placement), mice were euthanized, and corneas were imaged with confocal microscope (Leica TCS SP5), and assessed for number of labeled cDCs that were recruited
CD11c+ cDCs isolated from WT spleens were positive for chemokine receptor CXCR4 (42.1%); CD11c+ cDCs harvested from spleen of tumor mice showed prescence of CXCR4 in similar proportion (42.7%). In inflammation, corneas showed a significant increase in CD11c+ labeled cDCs in the stromal periphery and mid periphery/center compared to steady state (62±2 vs. 187±27 and 23±9 vs. 79±11 cells/mm2 respectively) (p<0.05, p<0.01). After blocking with anti-CXCR4 MAb, corneal stroma showed a significative decrease in CD11c+ cDC recruitment in the periphery and mid periphery/center (207±55 and 85±23 cells/mm2 respectively) compared to controls (388±51 and 153±19 cells/mm2) (p<0.05) (Mean±SEM).
CXCR4 is a chemokine receptor expressed by CD11c+ cDCs. The current study, is the first, to demonstrate a role for CXCR4 in the recruitment of cDC to the inflamed cornea, playing a direct role in dendritic cell homing after inflammation, making this receptor a potential target to modualte inflammatory responses in murine corneas.
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