The Murine Natural Cytotoxic Receptor NKp46/NCR1 Controls TRAIL Protein Expression in NK Cells and ILC1s

Sam Sheppard, Iona S. Schuster, Christopher E. Andoniou, Clement Cocita, Thomas Adejumo, Sam K.P. Kung, Joseph C. Sun, Mariapia A. Degli-Esposti, Nadia Guerra

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Abstract

TRAIL is an apoptosis-inducing ligand constitutively expressed on liver-resident type 1 innate lymphoid cells (ILC1s) and a subset of natural killer (NK) cells, where it contributes to NK cell anti-tumor, anti-viral, and immunoregulatory functions. However, the intrinsic pathways involved in TRAIL expression in ILCs remain unclear. Here, we demonstrate that the murine natural cytotoxic receptor mNKp46/NCR1, expressed on ILC1s and NK cells, controls TRAIL protein expression. Using NKp46-deficient mice, we show that ILC1s lack constitutive expression of TRAIL protein and that NK cells activated in vitro and in vivo fail to upregulate cell surface TRAIL in the absence of NKp46. We show that NKp46 regulates TRAIL expression in a dose-dependent manner and that the reintroduction of NKp46 in mature NK cells deficient for NKp46 is sufficient to restore TRAIL surface expression. These studies uncover a link between NKp46 and TRAIL expression in ILCs with potential implications in pathologies involving NKp46-expressing cells. Sheppard et al. find that mice deficient in the activating receptor NCR1/NKp46 (Ncr1−/−) fail to express the apoptosis-inducing ligand TRAIL at the surface of group 1 innate lymphoid cells (ILC1s).

Original languageEnglish
Pages (from-to)3385-3392
Number of pages8
JournalCell Reports
Volume22
Issue number13
DOIs
Publication statusPublished - 27 Mar 2018

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Sheppard, S., Schuster, I. S., Andoniou, C. E., Cocita, C., Adejumo, T., Kung, S. K. P., ... Guerra, N. (2018). The Murine Natural Cytotoxic Receptor NKp46/NCR1 Controls TRAIL Protein Expression in NK Cells and ILC1s. Cell Reports, 22(13), 3385-3392. https://doi.org/10.1016/j.celrep.2018.03.023