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

Victor S. Cortez, Tyler K. Ulland, Luisa Cervantes-Barragan, Jennifer K. Bando, Michelle L. Robinette, Qianli Wang, Andrew J. White, Susan Gilfillan, Marina Cella, Marco Colonna

Research output: Contribution to journalArticle

103 Scopus citations

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-β 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-β 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-β signaling mediated by the cytokine receptor TGFβR1 in NK cells. NK cells from a SMAD4-deficient person affected by polyposis were also hyper-responsive to TGF-β. These results identify SMAD4 as a previously unknown regulator that restricts non-canonical TGF-β signaling in NK cells.

Original languageEnglish
Pages (from-to)995-1003
Number of pages9
JournalNature immunology
Volume18
Issue number9
DOIs
StatePublished - Aug 22 2017

Fingerprint Dive into the research topics of 'SMAD4 impedes the conversion of NK cells into ILC1-like cells by curtailing non-canonical TGF-β signaling'. Together they form a unique fingerprint.

  • Cite this