Focus on mechanism of chronic ocular graft-vessus-host disease caused by donor-derived mesenchymal stem cells toward development of new treatment.

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Chronic ocular graft-versus-host disease(GVHD), i.e. chronic GVHD related dry eye, is a major complication after allogeneic hematopoietic stem cell transplantation. We have found that donor-derived mesenchymal stem cells play a significant role for underlying mechanism of chronic ocular GVHD fibrosis. We have found donor MSCs engrafted GVHD target organs such as lacrimal gland, conjunctiva, salivary gland, lung, skin, liver and intestine. We also suggested that donor MSCs interacted with T cells in the pathogenic regions and contributed to the onset of cGVHD and chronicity of this disease. We further showed donor MSCs increased IL-6 leading to decreased Tregs and conversely an increase in Th 17 cells in peripheral blood. Our results show that donor MSCs trigger immune responses in T cells and immune mediated fibrosis of chronic ocular GVHD.