Involvement of MST1/mTORC1/STAT1 activity in the regulation of B‐cell receptor signalling by chemokine receptor 2
Abstract Background CCR2 is involved in maintaining immune homeostasis and regulating immune function. This study aims to elucidate the mechanism by which CCR2 regulates B‐cell signalling. Methods In Ccr2‐knockout mice, the development and differentiation of B cells, BCR proximal signals, actin move...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
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Wiley
2022-07-01
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| Series: | Clinical and Translational Medicine |
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| Online Access: | https://doi.org/10.1002/ctm2.887 |
| _version_ | 1818179027737772032 |
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| author | Yingzi Zhu Heng Gu Lu Yang Na Li Qiuyue Chen Danqing Kang Shengyan Lin Yukai Jing Panpan Jiang Qianglin Chen Li Luo Ju Liu Jiang Chang Zhenzhen Li Yi Wang Xin Dai Heather Miller Lisa S. Westerberg Chan‐Sik Park Masato Kubo Quan Gong Lingli Dong Chaohong Liu |
| author_facet | Yingzi Zhu Heng Gu Lu Yang Na Li Qiuyue Chen Danqing Kang Shengyan Lin Yukai Jing Panpan Jiang Qianglin Chen Li Luo Ju Liu Jiang Chang Zhenzhen Li Yi Wang Xin Dai Heather Miller Lisa S. Westerberg Chan‐Sik Park Masato Kubo Quan Gong Lingli Dong Chaohong Liu |
| author_sort | Yingzi Zhu |
| collection | DOAJ |
| description | Abstract Background CCR2 is involved in maintaining immune homeostasis and regulating immune function. This study aims to elucidate the mechanism by which CCR2 regulates B‐cell signalling. Methods In Ccr2‐knockout mice, the development and differentiation of B cells, BCR proximal signals, actin movement and B‐cell immune response were determined. Besides, the level of CCR2 in PBMC of SLE patients was analysed by bioinformatics. Results CCR2 deficiency reduces the proportion and number of follicular B cells, upregulates BCR proximal signalling and enhances the oxidative phosphorylation of B cells. Meanwhile, increased actin filaments aggregation and its associated early‐activation events of B cells are also induced by CCR2 deficiency. The MST1/mTORC1/STAT1 axis in B cells is responsible for the regulation of actin remodelling, metabolic activities and transcriptional signalling, specific MST1, mTORC1 or STAT1 inhibitor can rescue the upregulated BCR signalling. Glomerular IgG deposition is obvious in CCR2‐deficient mice, accompanied by increased anti‐dsDNA IgG level. Additionally, the CCR2 expression in peripheral B cells of SLE patients is decreased than that of healthy controls. Conclusions CCR2 can utilise MST1/mTORC1/STAT1 axis to regulate BCR signalling. The interaction between CCR2 and BCR may contribute to exploring the mechanism of autoimmune diseases. |
| first_indexed | 2024-12-11T20:57:21Z |
| format | Article |
| id | doaj.art-69555a2cfdf646a39e3a520c73122fd2 |
| institution | Directory Open Access Journal |
| issn | 2001-1326 |
| language | English |
| last_indexed | 2024-12-11T20:57:21Z |
| publishDate | 2022-07-01 |
| publisher | Wiley |
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| series | Clinical and Translational Medicine |
| spelling | doaj.art-69555a2cfdf646a39e3a520c73122fd22022-12-22T00:51:04ZengWileyClinical and Translational Medicine2001-13262022-07-01127n/an/a10.1002/ctm2.887Involvement of MST1/mTORC1/STAT1 activity in the regulation of B‐cell receptor signalling by chemokine receptor 2Yingzi Zhu0Heng Gu1Lu Yang2Na Li3Qiuyue Chen4Danqing Kang5Shengyan Lin6Yukai Jing7Panpan Jiang8Qianglin Chen9Li Luo10Ju Liu11Jiang Chang12Zhenzhen Li13Yi Wang14Xin Dai15Heather Miller16Lisa S. Westerberg17Chan‐Sik Park18Masato Kubo19Quan Gong20Lingli Dong21Chaohong Liu22Department of Rheumatology and Immunology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Pathogen Biology, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Pathogen Biology, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Immunology, School of Medicine Yangtze University Jingzhou ChinaDepartment of Immunology, School of Medicine Yangtze University Jingzhou ChinaDepartment of Pathogen Biology, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Rheumatology and Immunology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Pathogen Biology, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Pathogen Biology, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Immunology, School of Medicine Yangtze University Jingzhou ChinaDepartment of Pathogen Biology, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Pathogen Biology, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Pathogen Biology, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Pathogen Biology, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Pathogen Biology, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Pathogen Biology, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Research and Development BD Biosciences San Jose California United StatesDepartment of Microbiology Tumor and Cell Biology Karolinska Institutet Stockholm SwedenDepartment of Pathology, Asan Medical Center University of Ulsan College of Medicine Songpa‐gu Seoul KoreaLaboratory for Cytokine Regulation, Center for Integrative Medical Science (IMS) RIKEN Yokohama Institute Kanagawa JapanDepartment of Immunology, School of Medicine Yangtze University Jingzhou ChinaDepartment of Rheumatology and Immunology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Pathogen Biology, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaAbstract Background CCR2 is involved in maintaining immune homeostasis and regulating immune function. This study aims to elucidate the mechanism by which CCR2 regulates B‐cell signalling. Methods In Ccr2‐knockout mice, the development and differentiation of B cells, BCR proximal signals, actin movement and B‐cell immune response were determined. Besides, the level of CCR2 in PBMC of SLE patients was analysed by bioinformatics. Results CCR2 deficiency reduces the proportion and number of follicular B cells, upregulates BCR proximal signalling and enhances the oxidative phosphorylation of B cells. Meanwhile, increased actin filaments aggregation and its associated early‐activation events of B cells are also induced by CCR2 deficiency. The MST1/mTORC1/STAT1 axis in B cells is responsible for the regulation of actin remodelling, metabolic activities and transcriptional signalling, specific MST1, mTORC1 or STAT1 inhibitor can rescue the upregulated BCR signalling. Glomerular IgG deposition is obvious in CCR2‐deficient mice, accompanied by increased anti‐dsDNA IgG level. Additionally, the CCR2 expression in peripheral B cells of SLE patients is decreased than that of healthy controls. Conclusions CCR2 can utilise MST1/mTORC1/STAT1 axis to regulate BCR signalling. The interaction between CCR2 and BCR may contribute to exploring the mechanism of autoimmune diseases.https://doi.org/10.1002/ctm2.887autoimmune diseasesB‐cell receptorCCR2MST1mTORC1 |
| spellingShingle | Yingzi Zhu Heng Gu Lu Yang Na Li Qiuyue Chen Danqing Kang Shengyan Lin Yukai Jing Panpan Jiang Qianglin Chen Li Luo Ju Liu Jiang Chang Zhenzhen Li Yi Wang Xin Dai Heather Miller Lisa S. Westerberg Chan‐Sik Park Masato Kubo Quan Gong Lingli Dong Chaohong Liu Involvement of MST1/mTORC1/STAT1 activity in the regulation of B‐cell receptor signalling by chemokine receptor 2 Clinical and Translational Medicine autoimmune diseases B‐cell receptor CCR2 MST1 mTORC1 |
| title | Involvement of MST1/mTORC1/STAT1 activity in the regulation of B‐cell receptor signalling by chemokine receptor 2 |
| title_full | Involvement of MST1/mTORC1/STAT1 activity in the regulation of B‐cell receptor signalling by chemokine receptor 2 |
| title_fullStr | Involvement of MST1/mTORC1/STAT1 activity in the regulation of B‐cell receptor signalling by chemokine receptor 2 |
| title_full_unstemmed | Involvement of MST1/mTORC1/STAT1 activity in the regulation of B‐cell receptor signalling by chemokine receptor 2 |
| title_short | Involvement of MST1/mTORC1/STAT1 activity in the regulation of B‐cell receptor signalling by chemokine receptor 2 |
| title_sort | involvement of mst1 mtorc1 stat1 activity in the regulation of b cell receptor signalling by chemokine receptor 2 |
| topic | autoimmune diseases B‐cell receptor CCR2 MST1 mTORC1 |
| url | https://doi.org/10.1002/ctm2.887 |
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