CX3CL1-induced CD16+ monocytes extravasation in myeloperoxidase-ANCA-associated vasculitis correlates with renal damage
BackgroundMonocytes are involved in the pathogenesis of ANCA-associated vasculitis (AAV). Monocyte/macrophages are the dominant infiltrating cells in the glomeruli of patients with myeloperoxidase-AAV (MPO-AAV). However, how human monocyte subsets extravasate to the kidney in MPO-AAV with renal dama...
Main Authors: | , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2022-08-01
|
Series: | Frontiers in Immunology |
Subjects: | |
Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.929244/full |
_version_ | 1811284144538255360 |
---|---|
author | Jiale Tang Jiale Tang Zhonghua Liao Liying Luo Shuanglinzi Deng Yuanyuan Jiang Fangyuan Wang Xinyue Hu Hongling Yin Guanghui Gong Juntao Feng Xiaozhao Li |
author_facet | Jiale Tang Jiale Tang Zhonghua Liao Liying Luo Shuanglinzi Deng Yuanyuan Jiang Fangyuan Wang Xinyue Hu Hongling Yin Guanghui Gong Juntao Feng Xiaozhao Li |
author_sort | Jiale Tang |
collection | DOAJ |
description | BackgroundMonocytes are involved in the pathogenesis of ANCA-associated vasculitis (AAV). Monocyte/macrophages are the dominant infiltrating cells in the glomeruli of patients with myeloperoxidase-AAV (MPO-AAV). However, how human monocyte subsets extravasate to the kidney in MPO-AAV with renal damage is unclear.Methods30 MPO-AAV patients with renal damage and 22 healthy controls were enrolled in this study. Monocyte subsets and monocyte-related chemokines in the blood and kidneys of MPO-AAV patients were detected. The chemoattractant activity of the CX3CL1-CX3CR1 axis on CD16+ monocytes was observed. The effect of MPO-ANCA on the migration of CD16+ monocytes to human glomerular endothelial cells (HGECs) was detected by flow cytometry and transwell migration assay.ResultsCompared with controls, CD16+ monocytes were significantly decreased in the blood and increased in the glomeruli of MPO-AAV patients with renal damage. The level of CX3CL1, but not CCL2, was significantly increased in the plasma of MPO-AAV patients. CX3CL1 co-localized with glomerular endothelial cells in MPO-AAV patients with renal damage. Moreover, we initially found that MPO-ANCA promotes an increase of the chemokine CX3CL1 on HGECs, imposing recruitment on CD16+ monocytes. Finally, the percentage of CD16+ monocytes in the blood was found to be positively correlated with estimated glomerular filtration rate (eGFR) and negatively correlated with urinary protein creatinine ratio in MPO-AAV patients with renal damage. Furthermore, the urinary protein creatinine ratio was positively correlated with the infiltrating of CD14+ and CD16+ cells in the kidneys.ConclusionEnhanced extravasation of CD16+ monocytes to the kidney via the CX3CL1-CX3CR1 axis may be involved in renal damage in MPO-AAV. |
first_indexed | 2024-04-13T02:24:13Z |
format | Article |
id | doaj.art-e5e1443a1b98427fb77d8079ddb4307f |
institution | Directory Open Access Journal |
issn | 1664-3224 |
language | English |
last_indexed | 2024-04-13T02:24:13Z |
publishDate | 2022-08-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Immunology |
spelling | doaj.art-e5e1443a1b98427fb77d8079ddb4307f2022-12-22T03:06:50ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-08-011310.3389/fimmu.2022.929244929244CX3CL1-induced CD16+ monocytes extravasation in myeloperoxidase-ANCA-associated vasculitis correlates with renal damageJiale Tang0Jiale Tang1Zhonghua Liao2Liying Luo3Shuanglinzi Deng4Yuanyuan Jiang5Fangyuan Wang6Xinyue Hu7Hongling Yin8Guanghui Gong9Juntao Feng10Xiaozhao Li11Department of Nephrology, Xiangya Hospital, Central South University, Changsha, ChinaCenter of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Nephrology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Nephrology, Xiangya Hospital, Central South University, Changsha, ChinaCenter of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, ChinaCenter of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Nephrology, Xiangya Hospital, Central South University, Changsha, ChinaCenter of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pathology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pathology, Xiangya Hospital, Central South University, Changsha, ChinaCenter of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Nephrology, Xiangya Hospital, Central South University, Changsha, ChinaBackgroundMonocytes are involved in the pathogenesis of ANCA-associated vasculitis (AAV). Monocyte/macrophages are the dominant infiltrating cells in the glomeruli of patients with myeloperoxidase-AAV (MPO-AAV). However, how human monocyte subsets extravasate to the kidney in MPO-AAV with renal damage is unclear.Methods30 MPO-AAV patients with renal damage and 22 healthy controls were enrolled in this study. Monocyte subsets and monocyte-related chemokines in the blood and kidneys of MPO-AAV patients were detected. The chemoattractant activity of the CX3CL1-CX3CR1 axis on CD16+ monocytes was observed. The effect of MPO-ANCA on the migration of CD16+ monocytes to human glomerular endothelial cells (HGECs) was detected by flow cytometry and transwell migration assay.ResultsCompared with controls, CD16+ monocytes were significantly decreased in the blood and increased in the glomeruli of MPO-AAV patients with renal damage. The level of CX3CL1, but not CCL2, was significantly increased in the plasma of MPO-AAV patients. CX3CL1 co-localized with glomerular endothelial cells in MPO-AAV patients with renal damage. Moreover, we initially found that MPO-ANCA promotes an increase of the chemokine CX3CL1 on HGECs, imposing recruitment on CD16+ monocytes. Finally, the percentage of CD16+ monocytes in the blood was found to be positively correlated with estimated glomerular filtration rate (eGFR) and negatively correlated with urinary protein creatinine ratio in MPO-AAV patients with renal damage. Furthermore, the urinary protein creatinine ratio was positively correlated with the infiltrating of CD14+ and CD16+ cells in the kidneys.ConclusionEnhanced extravasation of CD16+ monocytes to the kidney via the CX3CL1-CX3CR1 axis may be involved in renal damage in MPO-AAV.https://www.frontiersin.org/articles/10.3389/fimmu.2022.929244/fullantineutrophil cytoplasmic antibody (ANCA)-associated vasculitisCD16+ monocyteglomerular endothelial cellsCX3CL1renal damage |
spellingShingle | Jiale Tang Jiale Tang Zhonghua Liao Liying Luo Shuanglinzi Deng Yuanyuan Jiang Fangyuan Wang Xinyue Hu Hongling Yin Guanghui Gong Juntao Feng Xiaozhao Li CX3CL1-induced CD16+ monocytes extravasation in myeloperoxidase-ANCA-associated vasculitis correlates with renal damage Frontiers in Immunology antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis CD16+ monocyte glomerular endothelial cells CX3CL1 renal damage |
title | CX3CL1-induced CD16+ monocytes extravasation in myeloperoxidase-ANCA-associated vasculitis correlates with renal damage |
title_full | CX3CL1-induced CD16+ monocytes extravasation in myeloperoxidase-ANCA-associated vasculitis correlates with renal damage |
title_fullStr | CX3CL1-induced CD16+ monocytes extravasation in myeloperoxidase-ANCA-associated vasculitis correlates with renal damage |
title_full_unstemmed | CX3CL1-induced CD16+ monocytes extravasation in myeloperoxidase-ANCA-associated vasculitis correlates with renal damage |
title_short | CX3CL1-induced CD16+ monocytes extravasation in myeloperoxidase-ANCA-associated vasculitis correlates with renal damage |
title_sort | cx3cl1 induced cd16 monocytes extravasation in myeloperoxidase anca associated vasculitis correlates with renal damage |
topic | antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis CD16+ monocyte glomerular endothelial cells CX3CL1 renal damage |
url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.929244/full |
work_keys_str_mv | AT jialetang cx3cl1inducedcd16monocytesextravasationinmyeloperoxidaseancaassociatedvasculitiscorrelateswithrenaldamage AT jialetang cx3cl1inducedcd16monocytesextravasationinmyeloperoxidaseancaassociatedvasculitiscorrelateswithrenaldamage AT zhonghualiao cx3cl1inducedcd16monocytesextravasationinmyeloperoxidaseancaassociatedvasculitiscorrelateswithrenaldamage AT liyingluo cx3cl1inducedcd16monocytesextravasationinmyeloperoxidaseancaassociatedvasculitiscorrelateswithrenaldamage AT shuanglinzideng cx3cl1inducedcd16monocytesextravasationinmyeloperoxidaseancaassociatedvasculitiscorrelateswithrenaldamage AT yuanyuanjiang cx3cl1inducedcd16monocytesextravasationinmyeloperoxidaseancaassociatedvasculitiscorrelateswithrenaldamage AT fangyuanwang cx3cl1inducedcd16monocytesextravasationinmyeloperoxidaseancaassociatedvasculitiscorrelateswithrenaldamage AT xinyuehu cx3cl1inducedcd16monocytesextravasationinmyeloperoxidaseancaassociatedvasculitiscorrelateswithrenaldamage AT honglingyin cx3cl1inducedcd16monocytesextravasationinmyeloperoxidaseancaassociatedvasculitiscorrelateswithrenaldamage AT guanghuigong cx3cl1inducedcd16monocytesextravasationinmyeloperoxidaseancaassociatedvasculitiscorrelateswithrenaldamage AT juntaofeng cx3cl1inducedcd16monocytesextravasationinmyeloperoxidaseancaassociatedvasculitiscorrelateswithrenaldamage AT xiaozhaoli cx3cl1inducedcd16monocytesextravasationinmyeloperoxidaseancaassociatedvasculitiscorrelateswithrenaldamage |