Feehan, Karen T. and Bridgewater, Hannah E. and Stenkiewicz-Witeska, Jan and De Maeyer, Roel P. H. and Ferguson, John and Mack, Matthias and Brown, Jeremy and Ercoli, Giuseppe and Mawer, Connar M. and Akbar, Arne N. and Glanville, James R. W. and Jalali, Parinaaz and Bracken, Olivia V. and Nicolaou, Anna and Kendall, Alexandra C. and Sugimoto, Michelle A. and Gilroy, Derek W. (2024) Post-resolution macrophages shape long-term tissue immunity and integrity in a mouse model of pneumococcal pneumonia. NATURE COMMUNICATIONS, 15 (1): 4326. ISSN 2041-1723
Full text not available from this repository. (Request a copy)Abstract
Resolving inflammation is thought to return the affected tissue back to homoeostasis but recent evidence supports a non-linear model of resolution involving a phase of prolonged immune activity. Here we show that within days following resolution of Streptococcus pneumoniae-triggered lung inflammation, there is an influx of antigen specific lymphocytes with a memory and tissue-resident phenotype as well as macrophages bearing alveolar or interstitial phenotype. The transcriptome of these macrophages shows enrichment of genes associated with prostaglandin biosynthesis and genes that drive T cell chemotaxis and differentiation. Therapeutic depletion of post-resolution macrophages, inhibition of prostaglandin E2 (PGE2) synthesis or treatment with an EP4 antagonist, MF498, reduce numbers of lung CD4+/CD44+/CD62L+ and CD4+/CD44+/CD62L-/CD27+ T cells as well as their expression of the alpha-integrin, CD103. The T cells fail to reappear and reactivate upon secondary challenge for up to six weeks following primary infection. Concomitantly, EP4 antagonism through MF498 causes accumulation of lung macrophages and marked tissue fibrosis. Our study thus shows that PGE2 signalling, predominantly via EP4, plays an important role during the second wave of immune activity following resolution of inflammation. This secondary immune activation drives local tissue-resident T cell development while limiting tissue injury The post-resolution phase of inflammation is not simply a linear path towards cessation of immune response but rather a regulated process involving fluctuating immune activity. Here authors show a pivotal role for post-resolution macrophages in driving a wave of T cell recruitment and activation via prostaglandin E2 and alpha-integrin signalling during the resolution phase of murine pneumococcal pneumonia.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PROSTAGLANDIN-E-2 INHIBITS FIBROBLAST; PULMONARY FIBROSIS; RISK-FACTORS; INFLAMMATION; PROLIFERATION; GROWTH; LUNG; COMPLICATIONS; MODULATION |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Jan 2026 10:49 |
| Last Modified: | 27 Jan 2026 10:49 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65322 |
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