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Publication : IFN-γ-dependent regulation of intestinal epithelial homeostasis by NKT cells.

First Author  Lebrusant-Fernandez M Year  2024
Journal  Cell Rep Volume  43
Issue  12 Pages  114948
PubMed ID  39580798 Mgi Jnum  J:360817
Mgi Id  MGI:7852079 Doi  10.1016/j.celrep.2024.114948
Citation  Lebrusant-Fernandez M, et al. (2024) IFN-gamma-dependent regulation of intestinal epithelial homeostasis by NKT cells. Cell Rep 43(12):114948
abstractText  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 key 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 interferon-gamma (IFN-gamma) and interleukin-4 secretion. In vivo, lack of NKT cells results in an increase in IEC turnover, while NKT cell activation leads to IFN-gamma-dependent epithelial apoptosis. Our findings propose NKT cells as potent producers of cytokines that contribute to the regulation of IEC homeostasis.
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