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Misao Terada, Hiroko Taniguchi, Kazuichi Maruyama, Ryo Abe, Junko Hori; Inhibitory Role of ICOS on Corneal Lymphangiogenesis and Involvement of Foxp3+CD4+T Regulatory Cells in Secondary Lymphoid Organs. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4364.
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Interaction between the inducible costimulatory molecule (ICOS) and its ligand, B7-related protein (B7RP-1), has been reported to have an impact on differentiation and functions of various T regulatory cells. We have previously shown that blockade of ICOS/B7RP-1 led to an accelerated corneal allograft rejection. The purpose of the present study is to further investigate the role of ICOS on inflammatory lymphoangiogeneisis in the cornea and its mechanisms.
The mouse model of suture-induced inflammatory corneal neovascularization was used. After placement of sutures into the corneal stroma of ICOS-/- (BALB/c background) and W/T mice, hem- and lymphangiogenesis were evaluated using double immunohistochemistry of whole-mount corneas with CD31/PECAM1 as a panendothelial marker and LYVE-1 as a lymphatic endothelial marker. The areas of blood and lymphatic vessels in the inflamed cornea were analyzed and quantified using NIH image J software to compare the outgrowth of vessels between ICOS-/- and W/T mice. Spleen and cervical lymph node cells in these mice were also assessed for Foxp3+CD4+ cells by flow cytometry.
The outgrowth of blood and lymphatic vessels in ICOS-/- mice were statistical indistinguishable from those in W/T mice at 7 days. However, ICOS-/- mice developed significantly greater lymphatic vessels than W/T mice at 14 days (p<0.05). Whereas there was no difference in the proportion of Foxp3+cells in CD4+T cells of lymph nodes between ICOS-/- and W/T mice at 7 days, ICOS-/- mice showed a significantly lower proportion of these cells than W/T mice at 14 days. In splenic CD4+cells, the proportion of Foxp3+ cells in ICOS-/- mice was significantly lower than that in W/T mice at 7 and 14 days (p<0.01, p<0.05, respectively).
ICOS plays an inhibitory role on corneal inflammatory lymphangiogenesis. It is indicated that ICOS-mediated Foxp3+CD4+T regulatory cells developed in the secondary lymphoid organs may contribute to inhibit corneal lymphangiogenesis.
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