C3 deficiency promotes pulmonary inflammation in AT1R-induced mouse model for systemic sclerosis
IntroductionAutoantibody-mediated complement activation plays an essential role in a variety of autoimmune disorders. However, the role of complement in systemic sclerosis (SSc) remains largely unknown. In this study, we aimed to determine the role of complement C3 in the development of a recently d...
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1491324/full |
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| author | Junping Yin Admar Verschoor Admar Verschoor Xiaoyang Yue Xiaoyang Yue Torsten Goldmann Harald Heidecke Gabriela Riemekasten Frank Petersen Xinhua Yu |
| author_facet | Junping Yin Admar Verschoor Admar Verschoor Xiaoyang Yue Xiaoyang Yue Torsten Goldmann Harald Heidecke Gabriela Riemekasten Frank Petersen Xinhua Yu |
| author_sort | Junping Yin |
| collection | DOAJ |
| description | IntroductionAutoantibody-mediated complement activation plays an essential role in a variety of autoimmune disorders. However, the role of complement in systemic sclerosis (SSc) remains largely unknown. In this study, we aimed to determine the role of complement C3 in the development of a recently described SSc mouse model based on autoimmunity to angiotensin II receptor type 1 (AT1R).MethodsMice were immunized with cell membrane extract isolated from Chinese hamster ovary (CHO) cells overexpressing AT1R or non-transfected CHO cells as a control. Peripheral blood, dorsal skin and the lung were then collected to evlauate disease characteristics. Apoptotic cells in the lung of mice were detected using the DeadEnd™ Fluorometric TUNEL System.ResultsOur results showed that experimental SSc in this model was featured by the deposition of IgG, but not of complement C3, in the lung. After immunization with AT1R, C3-deficient mice developed more severe pulmonary inflammations than wild type controls, whereas skin inflammation and fibrosis were not different as well as the anti-AT1R ab levels. Further, C3-deficient mice showed an increased rate of pulmonary cell apoptosis as compared to controls. The apoptosis rate correlated with the corresponding degree of lung inflammation.DiscussionTaken together, our findings suggest an anti-apoptotic and anti-inflammatory role of complement C3 in pulmonary autoimmune inflammation. |
| format | Article |
| id | doaj-art-30cc61615da846b1a32d9144855a8d8f |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-30cc61615da846b1a32d9144855a8d8f2024-12-16T06:18:34ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-12-011510.3389/fimmu.2024.14913241491324C3 deficiency promotes pulmonary inflammation in AT1R-induced mouse model for systemic sclerosisJunping Yin0Admar Verschoor1Admar Verschoor2Xiaoyang Yue3Xiaoyang Yue4Torsten Goldmann5Harald Heidecke6Gabriela Riemekasten7Frank Petersen8Xinhua Yu9Priority Area Chronic Lung Diseases, Research Center Borstel - Leibniz Lung Center, Members of the German Center for Lung Research (DZL), Borstel, GermanyDepartment of Otorhinolaryngology, Technische Universität München and Klinikum Rechts der Isar, Munich, GermanyDepartment of Dermatology, University Clinic of Schleswig Holstein, University of Lübeck, Lübeck, GermanyPriority Area Chronic Lung Diseases, Research Center Borstel - Leibniz Lung Center, Members of the German Center for Lung Research (DZL), Borstel, GermanyCollege of Basic Medical Science, Key Laboratory of Basic Research on Regional Diseases, Education Department of Guangxi Zhuang Autonomous Region, Guangxi Medical University, Nanning, ChinaHistology, Research Center Borstel - Leibniz Lung Center, Members of the German Center for Lung Research (DZL), Borstel, GermanyCellTrend GmbH, Im Biotechnologiepark, Luckenwalde, GermanyDepartment of Rheumatology and Clinical Immunology, University Clinic of Schleswig Holstein, University of Lübeck, Lübeck, GermanyPriority Area Chronic Lung Diseases, Research Center Borstel - Leibniz Lung Center, Members of the German Center for Lung Research (DZL), Borstel, GermanyPriority Area Chronic Lung Diseases, Research Center Borstel - Leibniz Lung Center, Members of the German Center for Lung Research (DZL), Borstel, GermanyIntroductionAutoantibody-mediated complement activation plays an essential role in a variety of autoimmune disorders. However, the role of complement in systemic sclerosis (SSc) remains largely unknown. In this study, we aimed to determine the role of complement C3 in the development of a recently described SSc mouse model based on autoimmunity to angiotensin II receptor type 1 (AT1R).MethodsMice were immunized with cell membrane extract isolated from Chinese hamster ovary (CHO) cells overexpressing AT1R or non-transfected CHO cells as a control. Peripheral blood, dorsal skin and the lung were then collected to evlauate disease characteristics. Apoptotic cells in the lung of mice were detected using the DeadEnd™ Fluorometric TUNEL System.ResultsOur results showed that experimental SSc in this model was featured by the deposition of IgG, but not of complement C3, in the lung. After immunization with AT1R, C3-deficient mice developed more severe pulmonary inflammations than wild type controls, whereas skin inflammation and fibrosis were not different as well as the anti-AT1R ab levels. Further, C3-deficient mice showed an increased rate of pulmonary cell apoptosis as compared to controls. The apoptosis rate correlated with the corresponding degree of lung inflammation.DiscussionTaken together, our findings suggest an anti-apoptotic and anti-inflammatory role of complement C3 in pulmonary autoimmune inflammation.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1491324/fullsystemic sclerosisinflammationmouse modelcomplementpulmonary inflammation |
| spellingShingle | Junping Yin Admar Verschoor Admar Verschoor Xiaoyang Yue Xiaoyang Yue Torsten Goldmann Harald Heidecke Gabriela Riemekasten Frank Petersen Xinhua Yu C3 deficiency promotes pulmonary inflammation in AT1R-induced mouse model for systemic sclerosis Frontiers in Immunology systemic sclerosis inflammation mouse model complement pulmonary inflammation |
| title | C3 deficiency promotes pulmonary inflammation in AT1R-induced mouse model for systemic sclerosis |
| title_full | C3 deficiency promotes pulmonary inflammation in AT1R-induced mouse model for systemic sclerosis |
| title_fullStr | C3 deficiency promotes pulmonary inflammation in AT1R-induced mouse model for systemic sclerosis |
| title_full_unstemmed | C3 deficiency promotes pulmonary inflammation in AT1R-induced mouse model for systemic sclerosis |
| title_short | C3 deficiency promotes pulmonary inflammation in AT1R-induced mouse model for systemic sclerosis |
| title_sort | c3 deficiency promotes pulmonary inflammation in at1r induced mouse model for systemic sclerosis |
| topic | systemic sclerosis inflammation mouse model complement pulmonary inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1491324/full |
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