Vedder Nora, Gercke Philipp, Lautenschlager Nikoleta, Brunn Tobias, Lange Tim, Schieb Jakob, Vetter Charlotte, van Geffen Chiel, Kolahian Saeed
German Center for Lung Research (DZL), Universities of Giessen and Marburg Lung Center (UGMLC) Philipps University Marburg, Marburg, Germany.
Preclinical Imaging Core Facility, Center for Tumor Biology and Immunology (ZTI), Philipps University Marburg, Marburg, Germany.
FASEB J. 2025 May 31;39(10):e70626. doi: 10.1096/fj.202500312RR.
The immune system plays a major role in pulmonary fibrosis (PF), a devastating lung disease with limited treatment options. Myeloid-derived suppressor cells (MDSCs) are immune cells with remarkable immunosuppressive functions. We hypothesized that their anti-inflammatory activity may dampen PF by inhibiting inflammation and its transition to fibrosis. Here, we studied the emergence of both polymorphonuclear (PMN)- and monocytic (M)-MDSCs in a murine model of PF. We assessed immunological, histopathological, and clinical changes at days 3, 7, 14, and 21 following bleomycin challenge. A comprehensive overview of the role of MDSCs during the acute lung injury and chronic phase of pulmonary fibrosis is provided, along with the effects of MDSCs adoptive transfer and depletion. Inflammation and fibrosis increased over a period of 21 days after bleomycin administration. In the lung, the number of PMN-MDSCs increased, while M-MDSCs decreased over the time following bleomycin challenge. Especially, M-MDSCs showed enhanced suppressive activity on day 3 following bleomycin challenge. Adoptive transfer of PMN-MDSCs attenuated inflammation and fibrosis development. However, depletion of PMN-MDSCs did not lead to an exacerbation of PF. Our results suggest that adoptive transfer of PMN-MDSCs can ameliorate the inflammatory responses and thus the development of fibrosis in a bleomycin-induced pulmonary fibrosis model.
免疫系统在肺纤维化（PF）中起主要作用，肺纤维化是一种治疗选择有限的毁灭性肺部疾病。髓系来源的抑制性细胞（MDSCs）是具有显著免疫抑制功能的免疫细胞。我们假设它们的抗炎活性可能通过抑制炎症及其向纤维化的转变来减轻肺纤维化。在此，我们研究了PF小鼠模型中多形核（PMN）-MDSCs和单核（M）-MDSCs的出现情况。我们评估了博来霉素攻击后第3、7、14和21天的免疫、组织病理学和临床变化。本文提供了MDSCs在急性肺损伤和肺纤维化慢性期作用的全面概述，以及MDSCs过继转移和清除的效果。博来霉素给药后21天内，炎症和纤维化加剧。在肺中，博来霉素攻击后，PMN-MDSCs的数量增加，而M-MDSCs的数量减少。特别是，博来霉素攻击后第3天，M-MDSCs表现出增强的抑制活性。PMN-MDSCs的过继转移减弱了炎症和纤维化的发展。然而，清除PMN-MDSCs并未导致PF加重。我们的结果表明，PMN-MDSCs的过继转移可以改善炎症反应，从而减轻博来霉素诱导的肺纤维化模型中的纤维化发展。
