| Autor: |
Karen Feehan, Hannah Bridgewater, Jan Stenkiewicz-Witeska, John Ferguson, Matthias Mack, JEREMY BROWN, Giuseppe Ercoli, Connar Mawer, Arne Akbar, Parinaaz Jalali, Olivia Bracken, James Glanville, Anna Nicolaou, Alexandra Kendall, Michelle Sugimoto, Derek Gilroy |
| Rok vydání: |
2022 |
| Popis: |
Resolving inflammation is thought to return the affected tissue back to homeostasis. However, we show that within days following resolution of Streptococcus pneumonia-triggered lung inflammation there is an influx of antigen specific lymphocytes with a memory and tissue-resident phenotype as well as macrophages bearing an alveolar or interstitial phenotype. Transcriptomic analysis revealed that macrophages are enriched with genes that drive T cell chemotaxis and differentiation as well as prostaglandin biosynthesis. Therapeutic depletion of post-resolution macrophages or inhibition of PGE2/EP4 signalling reduced numbers of lung CD4+/CD44+/CD62L+ and CD4+/CD44+/CD62L-/CD27+ T cells as well as their expression of the alpha-integrin, CD103. This intervention resulted in a failure of these cells to reappear and reactivate upon secondary challenge up to six weeks following primary infection. Concomitantly, EP4 inhibition caused accumulation of lung macrophages and marked tissue fibrosis. Hence, resolving inflammation triggers a second wave of immune activity controlled, in part, by PGE2, which through EP4, drives local tissue-resident T cell development on the one hand, whilst limiting tissue injury on the other. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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