Acute invariant NKT cell activation triggers an immune response that drives prominent changes in iron homeostasis
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30 janvier 2023
- handle: 10670/1.tefo16
- doi: 10.1038/s41598-020-78037-3
Ce document est mis à disposition selon les termes de la Licence Creative Commons Paternité 4.0 International. / This work is licensed under a Creative Commons Attribution 4.0 International License. , https://creativecommons.org/licenses/by/4.0/
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Hua Huang et al., « Acute invariant NKT cell activation triggers an immune response that drives prominent changes in iron homeostasis », Papyrus : le dépôt institutionnel de l'Université de Montréal, ID : 10.1038/s41598-020-78037-3
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Résumé
Iron homeostasis is an essential biological process that ensures the tissue distribution of iron for various cellular processes. As the major producer of hepcidin, the liver is central to the regulation of iron metabolism. The liver is also home to many immune cells, which upon activation may greatly impact iron metabolism. Here, we focus on the role of invariant natural killer T (iNKT) cells, a subset of T lymphocytes that, in mice, is most abundant in the liver. Activation of iNKT cells with the prototypical glycosphingolipid antigen, α-galactosylceramide, resulted in immune cell proliferation and biphasic changes in iron metabolism. This involved an early phase characterized by hypoferremia, hepcidin induction and ferroportin suppression, and a second phase associated with strong suppression of hepcidin despite elevated levels of circulating and tissue iron. We further show that these changes in iron metabolism are fully dependent on iNKT cell activation. Finally, we demonstrate that the biphasic regulation of hepcidin is independent of NK and Kupfer cells, and is initially driven by the STAT3 infammatory pathway, whereas the second phase is regulated by repression of the BMP/SMAD signaling pathway. These fndings indicate that iNKT activation and the resulting cell proliferation infuence iron homeostasis.