AB0227 PSGL-1 deficiency develops systemic sclerosis in mice. (23rd January 2014)

• Record Type: Journal Article
• Authors: Urzainqui, A.; Perez-Frias, A.; Gonzalez-Tajuelo, R.; Nuñez-Andrade, N.; Tejedor, R.; Muñoz-Calleja, C.; Castañeda, S.; Vicente, E.; Gamallo, C.; Fraga, J.; García-Diez, A.
• Is Part Of: Annals of the rheumatic diseases. Volume 71(2012)Supplement 3
• Page Start: 650
• Page End: 650
• Publication Date: 2014-01-23
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2012-eular.227
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : 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