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Y. Ogawa, S. Shimmura, T. Kawakita, H. Okano, Y. Kawakami, K. Tsubota; Epithelial-Mesenchymal Transition of Conjunctival Basal Epithelia in Human Chronic Graft versus Host Disease. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5422. doi: https://doi.org/.
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Epithelial-mesenchymal transition (EMT) is involved in the development of various tissue fibrosis. TGF-β-dependent CD103 expression was reported to play a pivotal role in promoting GVHD by CD8+ T cells. We also found that T cell activation and excessive fibrosis contribute to the pathogenesis of dry eye associated with cGVHD. In this study, we investigated whether EMT contributed to conjunctival fibrosis and whether T cells were involved in the process.
Immunohistochemistry was used to observe CD4, CD8, CD103 expression as T cell markers, p63, E-cadherin expression as epithelial cell markers, and α-SMA, FSP-1, SNAIL, and HSP47 expression as mesenchymal cell markers. Conjunctival biopsies obtained from 9 patients with cGVHD were examined and compared with 5 normal conjunctival samples as control.
T cells expressing CD8 and CD103, a TGF-β-dependent ligand of E-cadherin, accumulated around the conjunctival basal epithelia of patients with cGVHD. Downregulation of E-cadherin, and translocation of β-catenin from the intercellular junction to the cytoplasm and nucleus were partially observed in the conjunctival basal epithelia of cGVHD. SNAIL was expressed in the nucleus of basal epithelial cells, especially in thick areas of the conjunctival epithelium suggesting that dissociation of basal epithelia at the site of GVHD mediated injury. HSP47 and α-SMA were also observed exclusively in the conjunctival basal epithelia. P63 expressing cells were observed in the subepithelial stroma. These observations were rarely observed in normal conjunctival epithelia.
Our findings suggested that intraepithelial T cell activation through CD103 and E cadherin interaction and subsequent EMT may be involved in the conjunctival fibrosis in patients with cGVHD.
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