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Distinct tissue niches direct lung immunopathology via CCL18 and CCL21 in severe COVID-19

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Item Type:Article
Title:Distinct tissue niches direct lung immunopathology via CCL18 and CCL21 in severe COVID-19
Creators Name:Mothes, R. and Pascual-Reguant, A. and Koehler, R. and Liebeskind, J. and Liebheit, A. and Bauherr, S. and Philipsen, L. and Dittmayer, C. and Laue, M. and von Manitius, R. and Elezkurtaj, S. and Durek, P. and Heinrich, F. and Heinz, G.A. and Guerra, G.M. and Obermayer, B. and Meinhardt, J. and Ihlow, J. and Radke, J. and Heppner, F.L. and Enghard, P. and Stockmann, H. and Aschman, T. and Schneider, J. and Corman, V.M. and Sander, L.E. and Mashreghi, M.F. and Conrad, T. and Hocke, A.C. and Niesner, R.A. and Radbruch, H. and Hauser, A.E.
Abstract:Prolonged lung pathology has been associated with COVID-19, yet the cellular and molecular mechanisms behind this chronic inflammatory disease are poorly understood. In this study, we combine advanced imaging and spatial transcriptomics to shed light on the local immune response in severe COVID-19. We show that activated adventitial niches are crucial microenvironments contributing to the orchestration of prolonged lung immunopathology. Up-regulation of the chemokines CCL21 and CCL18 associates to endothelial-to-mesenchymal transition and tissue fibrosis within these niches. CCL21 over-expression additionally links to the local accumulation of T cells expressing the cognate receptor CCR7. These T cells are imprinted with an exhausted phenotype and form lymphoid aggregates that can organize in ectopic lymphoid structures. Our work proposes immune-stromal interaction mechanisms promoting a self-sustained and non-resolving local immune response that extends beyond active viral infection and perpetuates tissue remodeling.
Keywords:CC Chemokines, CCR7 Receptors, COVID-19, Chemokine CCL21, Fibrosis, Lung, T-Lymphocytes
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:791
Date:11 February 2023
Official Publication:https://doi.org/10.1038/s41467-023-36333-2
PubMed:View item in PubMed

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