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The effect of NKT cell activation on the transcriptome of intestinal epithelial cells

GSE262526 Mus musculus Expression profiling by high throughput sequencing 9 samples Submitted 2024/11/25 Platform GPL24247
Summary
Intestinal homeostasis is maintained through the combined functions of epithelial and immune cells that collaborate to preserve the integrity of the intestinal barrier. However, the mechanisms by which immune cell populations regulate intestinal epithelial cell (IEC) homeostasis remain unclear. Here, we use a multi-omics approach to study the immune-epithelial crosstalk and identify CD1d-restricted Natural Killer T (NKT) cells as regulators of IEC biology. We find that NKT cells are abundant in the proximal small intestine and show hallmarks of activation at steady state. Subsequently, NKT cells regulate the survival and the transcriptional and cellular composition landscapes of IECs in intestinal organoids, through mechanisms dependent on IFN-γ and IL-4 secretion by NKT cells but independent of the expression of CD1d on IECs. In vivo, lack of NKT cells results in an increase in IEC turnover, while NKT cell activation leads to IFN-γ-dependent epithelial apoptosis. Our findings propose NKT cells as potent producers of cytokines that contribute to the regulation of IEC homeostasis.
Published in
IFN-γ-dependent regulation of intestinal epithelial homeostasis by NKT cells
Lebrusant-Fernandez M, Ap Rees T, Jimeno R et al. · Cell reports 2024 · PMID 39580798 · doi:10.1016/j.celrep.2024.114948
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Also filed as BioProject PRJNA1092120 and SRA study SRP498173. Searching any of these in the dataset finder brings you back here.

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