Heterogeneous ferroptosis susceptibility of macrophages caused by focal iron overload exacerbates rheumatoid arthritis
Focal iron overload is frequently observed in patients with rheumatoid arthritis (RA), yet its functional significance remains elusive. Herein, we report that iron deposition in lesion aggravates arthritis by inducing macrophage ferroptosis. We show that excessive iron in synovial fluid positively c...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231723004093 |
| _version_ | 1827400234183950336 |
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| author | Yan Liu Xiqing Luo Ye Chen Junlong Dang Donglan Zeng Xinghua Guo Weizhen Weng Jun Zhao Xiaoyi Shi Jingrong Chen Bo Dong Shuyuan Zhong Jianhua Ren Yuhang Li Julie Wang Jingwen Zhang Jianbo Sun Hanshi Xu Yan Lu David Brand Song Guo Zheng Yunfeng Pan |
| author_facet | Yan Liu Xiqing Luo Ye Chen Junlong Dang Donglan Zeng Xinghua Guo Weizhen Weng Jun Zhao Xiaoyi Shi Jingrong Chen Bo Dong Shuyuan Zhong Jianhua Ren Yuhang Li Julie Wang Jingwen Zhang Jianbo Sun Hanshi Xu Yan Lu David Brand Song Guo Zheng Yunfeng Pan |
| author_sort | Yan Liu |
| collection | DOAJ |
| description | Focal iron overload is frequently observed in patients with rheumatoid arthritis (RA), yet its functional significance remains elusive. Herein, we report that iron deposition in lesion aggravates arthritis by inducing macrophage ferroptosis. We show that excessive iron in synovial fluid positively correlates with RA disease severity as does lipid hyperoxidation of focal monocyte/macrophages. Further study reveals high susceptibility to iron induced ferroptosis of the anti-inflammatory macrophages M2, while pro-inflammatory M1 are less affected. Distinct glutathione peroxidase 4 (GPX4) degradation depending on p62/SQSTM1 in the two cell types make great contribution mechanically. Of note, ferroptosis inhibitor liproxstatin-1 (LPX-1) can alleviate the progression of K/BxN serum-transfer induced arthritis (STIA) mice accompanied with increasing M2 macrophages proportion. We thus propose that the heterogeneous ferroptosis susceptibility of macrophage subtypes as well as consequent inflammation and immune disorders are potential biomarkers and therapeutic targets in RA. |
| first_indexed | 2024-03-08T19:59:04Z |
| format | Article |
| id | doaj.art-531b221b3349458ab81a129d10c4b3ae |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-03-08T19:59:04Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-531b221b3349458ab81a129d10c4b3ae2023-12-24T04:45:29ZengElsevierRedox Biology2213-23172024-02-0169103008Heterogeneous ferroptosis susceptibility of macrophages caused by focal iron overload exacerbates rheumatoid arthritisYan Liu0Xiqing Luo1Ye Chen2Junlong Dang3Donglan Zeng4Xinghua Guo5Weizhen Weng6Jun Zhao7Xiaoyi Shi8Jingrong Chen9Bo Dong10Shuyuan Zhong11Jianhua Ren12Yuhang Li13Julie Wang14Jingwen Zhang15Jianbo Sun16Hanshi Xu17Yan Lu18David Brand19Song Guo Zheng20Yunfeng Pan21Department of Rheumatology and Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China; Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, ChinaDepartment of Rheumatology and Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, ChinaDepartment of Rheumatology and Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China; Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, ChinaDepartment of Pathology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, ChinaDepartment of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, ChinaDepartment of Rheumatology and Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, ChinaDepartment of Rheumatology and Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, ChinaDepartment of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, ChinaDepartment of Rheumatology and Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China; Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, ChinaDepartment of Rheumatology and Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China; Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, ChinaDepartment of Rheumatology and Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, ChinaDepartment of Rheumatology and Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, ChinaDepartment of Joint and Trauma Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, ChinaDepartment of Joint and Trauma Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, ChinaDivision of Rheumatology and Immunology, Department of Immunology, School of Cell and Gene Therapy, Songjiang Research Institute, Shanghai Songjiang District Central Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Hematology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, ChinaDepartment of Clinical Research, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, Guangdong, ChinaDepartment of Rheumatology and Immunology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, ChinaDepartment of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, ChinaThe Lt. Col. Luke Weathers, Jr. VA Medical Center, Memphis, TN, 38163, United StatesDivision of Rheumatology and Immunology, Department of Immunology, School of Cell and Gene Therapy, Songjiang Research Institute, Shanghai Songjiang District Central Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Corresponding author.Department of Rheumatology and Immunology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China; Corresponding author.Focal iron overload is frequently observed in patients with rheumatoid arthritis (RA), yet its functional significance remains elusive. Herein, we report that iron deposition in lesion aggravates arthritis by inducing macrophage ferroptosis. We show that excessive iron in synovial fluid positively correlates with RA disease severity as does lipid hyperoxidation of focal monocyte/macrophages. Further study reveals high susceptibility to iron induced ferroptosis of the anti-inflammatory macrophages M2, while pro-inflammatory M1 are less affected. Distinct glutathione peroxidase 4 (GPX4) degradation depending on p62/SQSTM1 in the two cell types make great contribution mechanically. Of note, ferroptosis inhibitor liproxstatin-1 (LPX-1) can alleviate the progression of K/BxN serum-transfer induced arthritis (STIA) mice accompanied with increasing M2 macrophages proportion. We thus propose that the heterogeneous ferroptosis susceptibility of macrophage subtypes as well as consequent inflammation and immune disorders are potential biomarkers and therapeutic targets in RA.http://www.sciencedirect.com/science/article/pii/S2213231723004093Rheumatoid arthritisIron overloadFerroptosisMacrophageGPX4 |
| spellingShingle | Yan Liu Xiqing Luo Ye Chen Junlong Dang Donglan Zeng Xinghua Guo Weizhen Weng Jun Zhao Xiaoyi Shi Jingrong Chen Bo Dong Shuyuan Zhong Jianhua Ren Yuhang Li Julie Wang Jingwen Zhang Jianbo Sun Hanshi Xu Yan Lu David Brand Song Guo Zheng Yunfeng Pan Heterogeneous ferroptosis susceptibility of macrophages caused by focal iron overload exacerbates rheumatoid arthritis Redox Biology Rheumatoid arthritis Iron overload Ferroptosis Macrophage GPX4 |
| title | Heterogeneous ferroptosis susceptibility of macrophages caused by focal iron overload exacerbates rheumatoid arthritis |
| title_full | Heterogeneous ferroptosis susceptibility of macrophages caused by focal iron overload exacerbates rheumatoid arthritis |
| title_fullStr | Heterogeneous ferroptosis susceptibility of macrophages caused by focal iron overload exacerbates rheumatoid arthritis |
| title_full_unstemmed | Heterogeneous ferroptosis susceptibility of macrophages caused by focal iron overload exacerbates rheumatoid arthritis |
| title_short | Heterogeneous ferroptosis susceptibility of macrophages caused by focal iron overload exacerbates rheumatoid arthritis |
| title_sort | heterogeneous ferroptosis susceptibility of macrophages caused by focal iron overload exacerbates rheumatoid arthritis |
| topic | Rheumatoid arthritis Iron overload Ferroptosis Macrophage GPX4 |
| url | http://www.sciencedirect.com/science/article/pii/S2213231723004093 |
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