| Autor: |
Ronja Mothes, Anna Pascual-Reguant, Ralf Koehler, Juliane Liebeskind, Alina Liebheit, Sandy Bauherr, Carsten Dittmayer, Michael Laue, Regina von Manitius, Sefer Elezkurtaj, Pawel Durek, Frederik Heinrich, Gitta Anne Heinz, Gabriela Maria Guerra, Benedikt Obermayer, Jenny Meinhardt, Jana Ihlow, Josefine Radke, Frank L. Heppner, Philipp Enghard, Helena Stockmann, Tom Aschman, Julia Schneider, Victor Corman, Leif Erik Sander, Mir-Farzin Mashreghi, Thomas Conrad, Andreas Hocke, Raluca A. Niesner, Helena Radbruch, Anja E. Hauser |
| Rok vydání: |
2022 |
| Popis: |
Post-acute lung sequelae of COVID-19 are challenging many survivors across the world, yet the mechanisms behind are poorly understood. Our results delineate an inflammatory cascade of events occurring along disease progression within fibrovascular niches. It is initiated by endothelial dysfunction, followed by heme scavenging of CD163+ macrophages and production of CCL18. This chemokine synergizes with local CCL21 upregulation to influence the stromal composition favoring endothelial to mesenchymal transition. The local immune response is further modulated via recruitment of CCR7+ T cells into the expanding fibrovascular niche and imprinting an exhausted, T follicular helper–like phenotype in these cells. Eventually, this culminates in the formation of tertiary lymphoid structures, further perpetuating chronic inflammation. Thus, our work presents misdirected immune-stromal interaction mechanisms promoting a self-sustained and non-resolving local immune response that extends beyond active viral infection and leads to profound tissue repurposing and chronic inflammation. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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