2. Academic Validation
  3. CD206+CD68+ mono-macrophages and serum soluble CD206 level are increased in antineutrophil cytoplasmic antibodies associated glomerulonephritis

CD206+CD68+ mono-macrophages and serum soluble CD206 level are increased in antineutrophil cytoplasmic antibodies associated glomerulonephritis

  • BMC Immunol. 2022 Nov 15;23(1):55. doi: 10.1186/s12865-022-00529-w.
Xiao-Ning An # 1 2,  Zhao-Nan Wei # 1,  Yin-Yin Xie # 3,  Jing Xu 1,  Yan Shen 4,  Li-Yan Ni 1,  Hao Shi 1,  Ping-Yan Shen 1 5,  Wen Zhang 1 5,  Yong-Xi Chen 6 7
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Nephrology, No. Six People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai, People's Republic of China.
  • 3 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.
  • 4 Research Center for Experimental Medicine, Ruijin Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai, People's Republic of China.
  • 5 Department of Nephrology, Xinrui Hospital, Ruijin Hospital Wuxi Branch, Wuxi, Jiangsu, People's Republic of China.
  • 6 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.
  • 7 Department of Nephrology, Xinrui Hospital, Ruijin Hospital Wuxi Branch, Wuxi, Jiangsu, People's Republic of China. rickychen@sjtu.edu.cn.
  • # Contributed equally.
PMID: 36376784 DOI: 10.1186/s12865-022-00529-w
Abstract

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.

Keywords

ANCA; Antineutrophil cytoplasmic antibodies; CD206; Glomerulonephritis; Mono-macrophage.

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