CD206+ mono-macrophages are involved in Antineutrophil Cytoplasmic Antibodies associated glomerulonephritis

Abstract BackgroundAntineutrophil Cytoplasmic Antibodies (ANCA) associated glomerulonephritis (AGN) is a group of autoimmune diseases and mono-macrophages are involved in its glomerular injuries. We investigate role of CD206+ mono-macrophages in AGN to provide therapeutic targets for the disease. Methods 27 AGN patients (14 active AGN, 13 remissive AGN) together with healthy controls (n=9), disease controls (n=6) and kidney function adjusted controls (n=9) from Department of Nephrology, Ruijin hospital were recruited. Flow cytometry was used to study proportion of CD206+ cells in peripheral blood. Immunohistochemistry for CD206 staining was performed in kidney tissues. Serum soluble CD206 (sCD206) was measured by enzyme-linked immunosorbent assay (ELISA). We also generated murine myeloperoxidase (MPO) (muMPO) ANCA by immunizing Mpo-/- mice. Mouse bone marrow-derived macrophages (BMDMs) and peripheral blood mononuclear cell (PBMC) derived macrophages were treated with MPO ANCA with or without its inhibitor AZD5904 to investigate the effects of MPO-ANCA on CD206 expression.ResultsThe proportion of peripheral CD206+CD68+ cells in active AGN patients were significantly higher than that in remissive patients (p<0.001), healthy controls (p<0.001) and kidney function adjusted controls (p<0.001). Serum sCD206 level in active AGN patients was higher than that in healthy controls (p<0.05) and remissive patients (p<0.01). Immunohistochemistry showed CD206 was highly expressed in the kidney tissues in active AGN patients in comparison with disease controls. Further studies showed MPO ANCA could induce CD206 expression in BMDMs and PBMC derived macrophages and such effects could be reversed by its inhibitor AZD5904. Conclusion ANCA could induce CD206 expression on mono-macrophages and CD206+ mono-macrophages are activated in AGN. Serum sCD206 correlates to disease activity and it could serve as a potential therapeutic target for the disease.