TY  - JOUR
AU  - Mothes, Ronja
AU  - Pascual-Reguant, Anna
AU  - Koehler, Ralf
AU  - Liebeskind, Juliane
AU  - Liebheit, Alina
AU  - Bauherr, Sandy
AU  - Philipsen, Lars
AU  - Dittmayer, Carsten
AU  - Laue, Michael
AU  - von Manitius, Regina
AU  - Elezkurtaj, Sefer
AU  - Durek, Pawel
AU  - Heinrich, Frederik
AU  - Heinz, Gitta A
AU  - Guerra, Gabriela M
AU  - Obermayer, Benedikt
AU  - Meinhardt, Jenny
AU  - Ihlow, Jana
AU  - Radke, Josefine
AU  - Heppner, Frank L
AU  - Enghard, Philipp
AU  - Stockmann, Helena
AU  - Aschman, Tom
AU  - Schneider, Julia
AU  - Corman, Victor M
AU  - Sander, Leif E
AU  - Mashreghi, Mir-Farzin
AU  - Conrad, Thomas
AU  - Hocke, Andreas C
AU  - Niesner, Raluca A
AU  - Radbruch, Helena
AU  - Hauser, Anja E
TI  - Distinct tissue niches direct lung immunopathology via CCL18 and CCL21 in severe COVID-19.
JO  - Nature Communications
VL  - 14
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DKFZ-2023-00325
SP  - 791
PY  - 2023
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:36774347
DO  - DOI:10.1038/s41467-023-36333-2
UR  - https://inrepo02.dkfz.de/record/267547
ER  -