Skip to main content

ORIGINAL RESEARCH article

Front. Immunol.
Sec. Molecular Innate Immunity
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1491324
This article is part of the Research Topic Community Series in the Role of Complement in Health and Disease: Volume II View all 10 articles

C3 deficiency promotes pulmonary inflammation in AT1R-induced mouse model for systemic sclerosis

Provisionally accepted
Junping Yin Junping Yin 1Admar Verschoor Admar Verschoor 2Xiaoyang Yue Xiaoyang Yue 1Harald Heidecke Harald Heidecke 3Gabriela Riemekasten Gabriela Riemekasten 4Frank Petersen Frank Petersen 1*Xinhua Yu Xinhua Yu 1*
  • 1 Research Center Borstel (LG), Borstel, Germany
  • 2 University Hospital rechts der Isar, Technical University of Munich, Munich, Bavaria, Germany
  • 3 CellTrend GmbH, Luckenwalde, Germany
  • 4 University of Lübeck, Lübeck, Schleswig-Holstein, Germany

The final, formatted version of the article will be published soon.

    Autoantibody-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). Mice 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. Aapoptotic cells in the lung of mice were detected using the DeadEnd™ Fluorometric TUNEL System. Our 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. Taken together, our findings suggest an anti-apoptotic and anti-inflammatory role of complement C3 in pulmonary autoimmune inflammation.

    Keywords: systemic sclerosis, Inflammation, mouse model, complement, pulmonary inflammation

    Received: 04 Sep 2024; Accepted: 29 Nov 2024.

    Copyright: © 2024 Yin, Verschoor, Yue, Heidecke, Riemekasten, Petersen and Yu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Frank Petersen, Research Center Borstel (LG), Borstel, 23845, Germany
    Xinhua Yu, Research Center Borstel (LG), Borstel, 23845, Germany

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.