Background Previous studies in our lab have established that PSGL-1 signaling in human monocyte-derived dendritic (DC) cells induces a tolerogenic program that enables them to promote the differentiation of naïve T cells to T regulatory cells (Treg). We have also found that PSGL-1 modulates the immune inflammatory response in the murine enteric lamina propria, indicating that this adhesion receptor plays a role in the control of peripheral tolerance, acting as a tolerogenic receptor.
Objectives To study the spontaneous disease developed in PSGL-1 deficient mice and and analyze its evolution with aging
Methods Inmunological study of skin infiltrate, Serological analysis and histological studies of skin, lungs and kidney of C57/Bl6 WT and PSGL-1 deficient mice
Results we have observed that 30% of PSGL-1 deficient mice at the age of 3 months present skin ulcers in their back that get more severe as the animals get older. The immunological studies show an inflammatory environment in the skin of the PSGL-1 KO mice, with activated and pro-inflammatory DC and macrophage populations, increased populations of granulocytes and B lymphocytes and increased Teff/Treg ratio. In addition, these animals cannot maintain the back legs extended, suggesting muscle weakness, and do not gain weight after the age of 1 year, probably due to intestinal absorption problems. The serum analysis shows the presence of connective tissue disease-related autoantibodies that accumulate as the mice get old. By histological studies we have found that the skin of PSGL-1 deficient mice is altered, with loss of the fat layer and thickening of the dermis by collagen accumulation, a major criterion supporting a diagnosis of Scleroderma. We have also found that the old PSGL-1 deficient mice have infiltrating leukocytes in the lungs and in the kidneys, indicating systemic autoimmune disease.
Conclusions All these data indicate that PSGL-1 has an important role in maintaining the homeostasis of the immune system and controlling the development of systemic sclerosis
Disclosure of Interest None Declared
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