Publikationsdatenbank

Distinct tissue niches direct lung immunopathology via CCL18 and CCL21 in severe COVID-19 (2023)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Mothes, Ronja

Pascual-Reguant, Anna

Koehler, Ralf

Liebeskind, Juliane (WE 6)

Liebheit, Alina

Bauherr, Sandy

Philipsen, Lars

Dittmayer, Carsten

Laue, Michael

von Manitius, Regina

Elezkurtaj, Sefer

Durek, Pawel

Heinrich, Frederik

Heinz, Gitta A.

Guerra, Gabriela M.

Obermayer, Benedikt

Meinhardt, Jenny

Ihlow, Jana

Radke, Josefine

Heppner, Frank L.

Enghard, Philipp

Stockmann, Helena

Aschman, Tom

Schneider, Julia

Corman, Victor M.

Sander, Leif E.

Mashreghi, Mir-Farzin

Conrad, Thomas (WE 12)

Hocke, Andreas C.

Niesner, Raluca A. (WE 2)

Radbruch, Helena

Hauser, Anja E.

Quelle

Nature Communications

Bandzählung: 14

Heftzählung: 1

Seiten: 791

ISSN: 2041-1723

Sprache

Englisch

Verweise

URL (Volltext): https://pubmed.ncbi.nlm.nih.gov/36774347/

DOI: 10.1038/s41467-023-36333-2

Pubmed: 36774347

Kontakt

Institut für Immunologie

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51834
immunologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.