| First Author | Cortez VS | Year | 2017 |
| Journal | Nat Immunol | Volume | 18 |
| Issue | 9 | Pages | 995-1003 |
| PubMed ID | 28759002 | Mgi Jnum | J:259299 |
| Mgi Id | MGI:6141246 | Doi | 10.1038/ni.3809 |
| Citation | Cortez VS, et al. (2017) SMAD4 impedes the conversion of NK cells into ILC1-like cells by curtailing non-canonical TGF-beta signaling. Nat Immunol 18(9):995-1003 |
| abstractText | 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-beta 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-beta 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-beta signaling mediated by the cytokine receptor TGFbetaR1 in NK cells. NK cells from a SMAD4-deficient person affected by polyposis were also hyper-responsive to TGF-beta. These results identify SMAD4 as a previously unknown regulator that restricts non-canonical TGF-beta signaling in NK cells. |
