SMAD4 impedes conversion of NK cells into ILC1-like cells by curtailing non-canonical TGFb signaling (human data sets). Homo sapiens

Among the features that distinguish type 1 innate lymphoid cells (ILC1s) from NK cells is a gene signature indicative of TGFb-family cytokine imprinting. To assess the impact of TGFb family cytokines on ILC1 differentation, we examined SMAD4- a transcription factor that facilitates the signaling pathway common to all TGFb family cytokines-was specifically ablated in ILCs and NK cells. While SMAD4 deficiency did not affect ILC1 differentation, NK cells paradoxically aquired an ILC1-like gene signature and were incapable of controlling tumor metastasis and viral infection. We used microarray to compare the transcriptional differences between human blood NK cells. NK cells from a patient with a deleterious SMAD4 mutation or control NK cells were cultured overnight with either IL-2 alone or TGFb1 and IL-2. Overall design: Sort purified blood NK cells (CD56+CD3-CD19-) from a patient with a deleterious SMAD4 mutation or a healthy control patient were expanded in cultured. Cells were then cultured overnight with either IL-2 alone or TGFb1 and IL-2.