| Title: |
CD163 and Tim-4 identify resident intestinal macrophages across sub-tissular regions that are spatially regulated by TGF-β |
| Authors: |
Prise, Ian E.; Jayaraman, Vignesh; Kästele, Verena; Daw, Rufus H.; Wemyss, Kelly; Bridgeman, Hayley; Tamburrano, Sabrina; Strangward, Patrick; Chew, Christine; Martens, Liesbet; Scott, Charlotte L.; Guilliams, Martin; Adamson, Antony D.; Konkel, Joanne E.; Shaw, Tovah N.; Grainger, John R. |
| Source: |
Prise, I E, Jayaraman, V, Kästele, V, Daw, R H, Wemyss, K, Bridgeman, H, Tamburrano, S, Strangward, P, Chew, C, Martens, L, Scott, C L, Guilliams, M, Adamson, A D, Konkel, J E, Shaw, T N & Grainger, J R 2023 'CD163 and Tim-4 identify resident intestinal macrophages across sub-tissular regions that are spatially regulated by TGF-β' bioRxiv. https://doi.org/10.1101/2023.08.21.553672 |
| Publisher Information: |
bioRxiv |
| Publication Year: |
2023 |
| Collection: |
The University of Manchester: Research Explorer - Publications |
| Subject Terms: |
immunology |
| Description: |
In bodily organs, macrophages are localised in poorly understood tissular and sub-tissular niches associated with defined macrophage ontogeny and activity. In the intestine, a paradigm is emerging that long-lived macrophages are dominantly present in the muscular layer, while highly monocyte-replenished populations are found in the lamina propria beneath the epithelial barrier. Whether longevity is restricted in such a simplified manner has not been well explored. Moreover, the impact of specific gut-associated factors on long-lived macrophage functionality and niche occupancy is unknown. We generated sc-RNA-Seq data from wild-type and Ccr2 − / − mice to identify phenotypic features of long-lived macrophage populations in distinct intestinal niches and identified CD163 as a useful marker to distinguish submucosal/muscularis (S/M) from lamina propria (LP) macrophages. Challenging the emerging paradigm, long-lived macrophages, identified by Tim-4 expression, were found in the LP and S/M. Long-lived LP macrophages are restrained in their response to proinflammatory stimulation compared to short-lived populations in the same location, and to the long-lived population within the S/M. Employing a novel Timd4 cre Tgfbr2 fl/fl mouse line we demonstrate distinct functions of TGF-β on long-lived macrophages in these two compartments. Importantly, in Timd4 cre Tgfbr2 fl/fl mice, zonation of CD163 + macrophages in the S/M was lost, suggesting TGF-β plays an unappreciated role in positioning of macrophages in the tissue. These data highlight the importance of considering ontogeny and niche when assessing the action of key intestinal regulatory signals. |
| Document Type: |
report |
| Language: |
English |
| DOI: |
10.1101/2023.08.21.553672 |
| Availability: |
https://research.manchester.ac.uk/en/publications/e365d941-579e-47b9-ad0b-d4b22fdf29da; https://doi.org/10.1101/2023.08.21.553672 |
| Rights: |
info:eu-repo/semantics/restrictedAccess ; http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.B20ABF59 |
| Database: |
BASE |