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Updated: Jun 14, 2025
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Co-Culture of Murine Small Intestine Epithelial Organoids with Innate Lymphoid Cells
Published on: March 23, 2022
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Recipient tissue microenvironment determines developmental path of intestinal innate lymphoid progenitors
Paula A Clark1, Mayuri Gogoi2, Noe Rodriguez-Rodriguez2
1MRC Laboratory of Molecular Biology, Cambridge, United Kingdom. pclark@mrc-lmb.cam.ac.uk.
Nature Communications
|September 6, 2024
Summary
A rare innate lymphoid cell progenitor (ILCP) in the small intestine can generate diverse ILCs locally. However, its potential is restricted in other tissues, showing microenvironment influences immune cell development.
Area of Science:
- Immunology
- Cell Biology
- Developmental Biology
Background:
- Innate lymphoid cells (ILCs) are crucial for tissue homeostasis, infection, and inflammation.
- Understanding ILC progenitor (ILCP) potential is key to immune regulation.
Purpose of the Study:
- To identify and characterize a rare ILCP population in the adult mouse small intestinal lamina propria (siLP).
- To investigate the differentiation potential of siLP-ILCPs in various tissue microenvironments.
Main Methods:
- Combinatorial reporter mice for ILCP identification.
- Cell transfer experiments into recipient mice.
- Single-cell gene expression analysis.
- High-dimensional spectral cytometry.
Main Results:
- siLP-ILCPs generate group 1 ILCs, ILC2s, and ILC3s in the intestinal microenvironment.
- In liver, lung, and spleen, siLP-ILCPs predominantly generate group 1 ILCs.
- Tissue microenvironment influences the phenotype of group 1 ILC progeny.
- siLP-ILCPs show distinct potential compared to bone marrow-derived ILCPs, favoring ILC1 and ILC3.
Conclusions:
- A local pool of siLP-ILCP contributes to diverse ILC generation within the intestine.
- ILCP potential is shaped by both tissue of origin and the developmental microenvironment.
- This plasticity offers flexibility in tuning immune responses.
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