SMAD4 impedes the conversion of NK cells into ILC1-like cells by curtailing non-canonical TGF-? signaling.

ABSTRACT: Among the features that distinguish type 1 innate lymphoid cells (ILC1s) from natural killer (NK) cells is a gene signature indicative of 'imprinting' by cytokines of the TGF-? family. We studied mice in which ILC1s and NK cells lacked SMAD4, a signal transducer that facilitates the canonical signaling pathway common to all cytokines of the TGF-? family. While SMAD4 deficiency did not affect ILC1 differentiation, NK cells unexpectedly acquired an ILC1-like gene signature and were unable to control tumor metastasis or viral infection. Mechanistically, SMAD4 restrained non-canonical TGF-? signaling mediated by the cytokine receptor TGF?R1 in NK cells. NK cells from a SMAD4-deficient person affected by polyposis were also hyper-responsive to TGF-?. These results identify SMAD4 as a previously unknown regulator that restricts non-canonical TGF-? signaling in NK cells.

SUBMITTER: Cortez VS 

PROVIDER: S-EPMC5712491 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature