Recipient tissue microenvironment determines developmental path of intestinal innate lymphoid progenitors

Paula A. Clark (), Mayuri Gogoi, Noe Rodriguez-Rodriguez, Ana C. F. Ferreira, Jane E. Murphy, Jennifer A. Walker, Alastair Crisp, Helen E. Jolin, Jacqueline D. Shields and Andrew N. J. McKenzie ()
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Paula A. Clark: MRC Laboratory of Molecular Biology
Mayuri Gogoi: MRC Laboratory of Molecular Biology
Noe Rodriguez-Rodriguez: MRC Laboratory of Molecular Biology
Ana C. F. Ferreira: MRC Laboratory of Molecular Biology
Jane E. Murphy: MRC Laboratory of Molecular Biology
Jennifer A. Walker: MRC Laboratory of Molecular Biology
Alastair Crisp: MRC Laboratory of Molecular Biology
Helen E. Jolin: MRC Laboratory of Molecular Biology
Jacqueline D. Shields: University of Nottingham Biodiscovery Institute
Andrew N. J. McKenzie: MRC Laboratory of Molecular Biology

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Innate lymphoid cells (ILCs) are critical in maintaining tissue homeostasis, and during infection and inflammation. Here we identify, by using combinatorial reporter mice, a rare ILC progenitor (ILCP) population, resident to the small intestinal lamina propria (siLP) in adult mice. Transfer of siLP-ILCP into recipients generates group 1 ILCs (including ILC1 and NK cells), ILC2s and ILC3s within the intestinal microenvironment, but almost exclusively group 1 ILCs in the liver, lung and spleen. Single cell gene expression analysis and high dimensional spectral cytometry analysis of the siLP-ILCPs and ILC progeny indicate that the phenotype of the group 1 ILC progeny is also influenced by the tissue microenvironment. Thus, a local pool of siLP-ILCP can contribute to pan-ILC generation in the intestinal microenvironment but has more restricted potential in other tissues, with a greater propensity than bone marrow-derived ILCPs to favour ILC1 and ILC3 production. Therefore, ILCP potential is influenced by both tissue of origin and the microenvironment during development. This may provide additional flexibility during the tuning of immune reactions.

Date: 2024
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DOI: 10.1038/s41467-024-52155-2

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