GSE264058 Post-resolution macrophage-derived lipids shapes long-term tissue immunity and integrity

Contributors : Karen T Feehan ; Hannah E Bridgewater ; Jan Stenkiewicz-Witeska ; Roel P De Maeyer ; John Ferguson ; Matthias Mack ; Jemery Brown ; Giuseppe Ercoli ; Connar M Mawer ; Arne N Akbar ; James R Glanville ; Parinaaz Jalali ; Olivia V Bracken ; Anna Nicolaou ; Alexandra C Kendall ; Michelle A Sugimoto ; Derek W GilorySeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusResolving 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, inhibition of PGE2 synthesis or antagonism of EP4 reduced numbers of lung CD4+/CD44+/CD62L+ and CD4+/CD44+/CD62L-/CD27+ T cells as well as their expression of the a-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 antagonism caused accumulation of lung macrophages and marked tissue fibrosis. Hence, resolving inflammation triggers a second wave of immune activit...

Source: GEO: Gene Expression Omnibus - April 17, 2024 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research