Profibrotic monocyte-derived alveolar macrophages are expanded in patients with persistent respiratory symptoms and radiographic abnormalities after COVID-19
Joseph I. Bailey, Connor H. Puritz, Karolina J. Senkow, Nikolay S. Markov, Estefani Diaz, Emmy Jonasson, Zhan Yu, Suchitra Swaminathan, Ziyan Lu, Samuel Fenske, Rogan A. Grant, Hiam Abdala-Valencia, Ruben J. Mylvaganam, Amy Ludwig, Janet Miller, R. Ian Cumming, Robert M. Tighe, Kymberly M. Gowdy, Ravi Kalhan, Manu Jain, Ankit Bharat, Chitaru Kurihara, Ruben San Jose Estepar, Raul San Jose Estepar, George R. Washko, Ali Shilatifard, Jacob I. Sznajder, Karen M. Ridge, G. R. Scott Budinger, Rosemary Braun, Alexander V. Misharin, Marc A. Sala
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引用次数: 0
Abstract
Monocyte-derived alveolar macrophages drive lung injury and fibrosis in murine models and are associated with pulmonary fibrosis in humans. Monocyte-derived alveolar macrophages have been suggested to develop a phenotype that promotes lung repair as injury resolves. We compared single-cell and cytokine profiling of the alveolar space in a cohort of 35 patients with post-acute sequelae of COVID-19 who had persistent respiratory symptoms and abnormalities on a computed tomography scan of the chest that subsequently improved or progressed. The abundance of monocyte-derived alveolar macrophages, their gene expression programs, and the level of the monocyte chemokine CCL2 in bronchoalveolar lavage fluid positively associated with the severity of radiographic fibrosis. Monocyte-derived alveolar macrophages from patients with resolving or progressive fibrosis expressed the same set of profibrotic genes. Our findings argue against a distinct reparative phenotype in monocyte-derived alveolar macrophages, highlighting their utility as a biomarker of failed lung repair and a potential target for therapy. Misharin, Sala and colleagues show that in patients with lung fibrosis after COVID-19, monocyte-derived alveolar macrophages activate an inflammatory and fibrotic program that was similar in patients with either resolving or progressing fibrosis.
期刊介绍:
Nature Immunology is a monthly journal that publishes the highest quality research in all areas of immunology. The editorial decisions are made by a team of full-time professional editors. The journal prioritizes work that provides translational and/or fundamental insight into the workings of the immune system. It covers a wide range of topics including innate immunity and inflammation, development, immune receptors, signaling and apoptosis, antigen presentation, gene regulation and recombination, cellular and systemic immunity, vaccines, immune tolerance, autoimmunity, tumor immunology, and microbial immunopathology. In addition to publishing significant original research, Nature Immunology also includes comments, News and Views, research highlights, matters arising from readers, and reviews of the literature. The journal serves as a major conduit of top-quality information for the immunology community.