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

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.

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Cortez VS, Ulland TK, Cervantes-Barragan L, Bando JK, Robinette ML, Wang Q, White AJ, Gilfillan S, Cella M, Colonna M