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Isolation and Characterization of Dendritic Cells and Macrophages from the Mouse Intestine
Published on: May 21, 2012
CD163 and Tim-4 identify resident intestinal macrophages that are spatially regulated by TGF-β
Vignesh Jayaraman1, Ian E Prise2, Verena Kästele2
1Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh , Edinburgh, UK.
Abstract:
Macrophages localize in sub-tissular niches associated with their ontogeny and activity. In the intestine, a paradigm has emerged that long-lived macrophages are present in the muscular layer, while highly monocyte-replenished populations are found in the lamina propria (LP). Whether long-lived macrophages are restricted in such a simplified manner has not been well explored. Moreover, the impact of specific gut-associated factors on macrophage identity across intestinal tissue layers is unknown. We generated scRNA-seq data from WT and Ccr2-/- mice to identify phenotypic features of long-lived macrophage populations in distinct intestinal layers and identified CD163 as a marker to distinguish submucosal/muscularis (S/M) from LP macrophages. Challenging the emerging paradigm, long-lived macrophages were found in the LP and S/M, with distinct transcriptomes and responsiveness to proinflammatory stimuli. Employing transgenic mice, we demonstrate a critical role for TGF-β signalling in maintaining the identity of long-lived LP but not S/M macrophages and that macrophage-derived TGF-β1 is required to instruct intestinal macrophage identity after development.
Insights
Long-lived intestinal macrophages reside in both the lamina propria and submucosal/muscular layers. Transforming growth factor-beta (TGF-β) signaling is crucial for maintaining the identity of these long-lived lamina propria macrophages.
Area of Science:
- Immunology
- Gastroenterology
- Cell Biology
Background:
- Macrophages are key immune cells found in various tissue layers.
- A prevailing model suggests distinct intestinal macrophage populations based on location and origin.
- The precise distribution and regulation of long-lived intestinal macrophages remain incompletely understood.
Purpose of the Study:
- To investigate the distribution and characteristics of long-lived macrophages across different intestinal tissue layers.
- To identify molecular factors influencing macrophage identity in the intestine.
- To challenge and refine the existing paradigm of intestinal macrophage compartmentalization.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) was performed on wild-type (WT) and Ccr2-/- mice.
- CD163 was identified as a marker to differentiate submucosal/muscularis (S/M) from lamina propria (LP) macrophages.
- Transgenic mouse models were utilized to study the role of TGF-β signaling.
Main Results:
- Long-lived macrophages were identified in both the LP and S/M layers, contrary to simplified models.
- Distinct transcriptomic profiles and inflammatory responses were observed between LP and S/M long-lived macrophages.
- TGF-β signaling was found to be essential for maintaining the identity of long-lived LP macrophages, but not S/M macrophages.
Conclusions:
- The distribution of long-lived intestinal macrophages is more complex than previously thought.
- Macrophage-derived TGF-β1 plays a critical role in establishing and maintaining intestinal macrophage identity post-development.
- Understanding these distinct macrophage populations and regulatory mechanisms is vital for intestinal health and disease.
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