PMID- 36376784 OWN - NLM STAT- MEDLINE DCOM- 20221120 LR - 20221222 IS - 1471-2172 (Electronic) IS - 1471-2172 (Linking) VI - 23 IP - 1 DP - 2022 Nov 15 TI - CD206(+)CD68(+) mono-macrophages and serum soluble CD206 level are increased in antineutrophil cytoplasmic antibodies associated glomerulonephritis. PG - 55 LID - 10.1186/s12865-022-00529-w [doi] LID - 55 AB - BACKGROUND: Antineutrophil Cytoplasmic Antibodies (ANCA) associated glomerulonephritis (AGN) is a group of autoimmune diseases and mono-macrophages are involved in its glomerular injuries. In this study, we aim to investigate the role of CD206(+) mono-macrophages in AGN. 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 and CD206 expression was scored in different kidney regions. 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) from wild C57BL/6 mice and peripheral blood mononuclear cell (PBMC) derived macrophages from healthy donors were treated with MPO ANCA with or without its inhibitor AZD5904 to investigate the effects of MPO-ANCA on CD206 expression. RESULTS: The 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 different kidney regions including fibrinoid necrosis or crescent formation, glomeruli, periglomerular and tubulointerstitial compartment 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. CD206 might be involved in the pathogenesis of AAV and may be a potential target for the disease. CI - (c) 2022. The Author(s). FAU - An, Xiao-Ning AU - An XN AD - Department of Nephrology, Ruijin Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, No. 197, Ruijin Er Rd, Shanghai, 200025, People's Republic of China. AD - Department of Nephrology, No. Six People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai, People's Republic of China. FAU - Wei, Zhao-Nan AU - Wei ZN AD - Department of Nephrology, Ruijin Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, No. 197, Ruijin Er Rd, Shanghai, 200025, People's Republic of China. FAU - Xie, Yin-Yin AU - Xie YY AD - Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China. FAU - Xu, Jing AU - Xu J AD - Department of Nephrology, Ruijin Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, No. 197, Ruijin Er Rd, Shanghai, 200025, People's Republic of China. FAU - Shen, Yan AU - Shen Y AD - Research Center for Experimental Medicine, Ruijin Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai, People's Republic of China. FAU - Ni, Li-Yan AU - Ni LY AD - Department of Nephrology, Ruijin Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, No. 197, Ruijin Er Rd, Shanghai, 200025, People's Republic of China. FAU - Shi, Hao AU - Shi H AD - Department of Nephrology, Ruijin Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, No. 197, Ruijin Er Rd, Shanghai, 200025, People's Republic of China. FAU - Shen, Ping-Yan AU - Shen PY AD - Department of Nephrology, Ruijin Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, No. 197, Ruijin Er Rd, Shanghai, 200025, People's Republic of China. AD - Department of Nephrology, Xinrui Hospital, Ruijin Hospital Wuxi Branch, Wuxi, Jiangsu, People's Republic of China. FAU - Zhang, Wen AU - Zhang W AD - Department of Nephrology, Ruijin Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, No. 197, Ruijin Er Rd, Shanghai, 200025, People's Republic of China. AD - Department of Nephrology, Xinrui Hospital, Ruijin Hospital Wuxi Branch, Wuxi, Jiangsu, People's Republic of China. FAU - Chen, Yong-Xi AU - Chen YX AD - Department of Nephrology, Ruijin Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, No. 197, Ruijin Er Rd, Shanghai, 200025, People's Republic of China. rickychen@sjtu.edu.cn. AD - Department of Nephrology, Xinrui Hospital, Ruijin Hospital Wuxi Branch, Wuxi, Jiangsu, People's Republic of China. rickychen@sjtu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221115 PL - England TA - BMC Immunol JT - BMC immunology JID - 100966980 RN - 0 (Antibodies, Antineutrophil Cytoplasmic) RN - EC 1.11.1.7 (Peroxidase) RN - 0 (MRC1 protein, human) SB - IM MH - Animals MH - Mice MH - *Antibodies, Antineutrophil Cytoplasmic MH - *Glomerulonephritis/metabolism/pathology MH - Leukocytes, Mononuclear/metabolism MH - Macrophages/metabolism MH - Mice, Inbred C57BL MH - Peroxidase/metabolism PMC - PMC9664714 OTO - NOTNLM OT - ANCA OT - Antineutrophil cytoplasmic antibodies OT - CD206 OT - Glomerulonephritis OT - Mono-macrophage COIS- Not applicable. EDAT- 2022/11/16 06:00 MHDA- 2022/11/18 06:00 PMCR- 2022/11/15 CRDT- 2022/11/15 00:06 PHST- 2022/07/25 00:00 [received] PHST- 2022/10/29 00:00 [accepted] PHST- 2022/11/15 00:06 [entrez] PHST- 2022/11/16 06:00 [pubmed] PHST- 2022/11/18 06:00 [medline] PHST- 2022/11/15 00:00 [pmc-release] AID - 10.1186/s12865-022-00529-w [pii] AID - 529 [pii] AID - 10.1186/s12865-022-00529-w [doi] PST - epublish SO - BMC Immunol. 2022 Nov 15;23(1):55. doi: 10.1186/s12865-022-00529-w.