653. Systemic High Mobility Group Box 1 Administration Suppresses Skin Inflammation By Inducing Accumulation of PDGFRα+ Mesenchymal Cells from Bone Marrow

High-mobility group box 1 (HMGB1), which is released by necrotic tissue, mobilises platelet-derived growth factor receptor alpha-positive (PDGFRα+) mesenchymal cells from bone marrow (BM) into circulation as a rescue signal. However, whether circulating HMGB1-induced endogenous PDGFRα+ mesenchymal cells stimulate skin regeneration has been unclear. Here we investigated the functions of the HMGB1/BM-PDGFRα+ mesenchymal cell axis in the regeneration of mouse skin grafts. We found that intravenous HMGB1 administration induced an accumulation of endogenous BM-PDGFRα+ mesenchymal cells followed by significant inflammatory suppression in the grafts. In contrast, mice with reduced BM-PDGFRα+ mesenchymal cells showed massive inflammation of skin grafts compared to mice that had normal levels of PDGFRα+ mesenchymal cells. This was true even when HMGB1 was administered, suggesting that endogenous PDGFRα+ mesenchymal cells contribute to the HMGB1-induced anti-inflammatory effect. We also found that intravenously administered HMGB1 augmented the local migration of BM-PDGFRα+ mesenchymal cells from circulation to skin graft by inducing the expression of CXCR4, an SDF-1 receptor, on BM-PDGFRα+ mesenchymal cells. We additionally investigated the therapeutic activity of the HMGB1/PDGFRα+ mesenchymal cell axis in inflammatory skin diseases using an allergic contact dermatitis model. The results illustrated the pivotal role of the HMGB1/BM-PDGFRα+ mesenchymal cells axis in suppressing the inflammation of injured/inflamed skin. These findings may provide future perspectives on the use of HMGB1-based medicines for intractable diseases.