Loss-of-Function in SMAD4 Might Not Be Critical for Human Natural Killer Cell Responsiveness to TGF-β

Lachlan P. Healy, Gustavo R. Rossi, Jai Rautela, Charlotte A. Slade, Nicholas D. Huntington, Ingrid M. Winship, Fernando Souza-Fonseca-Guimaraes

Research output: Contribution to journalArticleOtherpeer-review


We characterized the NK cell phenotype and function in three family members with Hereditary Hemorrhagic Telangiectasia (HHT) due to heterozygous SMAD4 mutations. Loss-of-function mutation in this gene did not induce developmental effects to alter CD56bright or CD56dim NK cell subset proportions in peripheral blood; and did not result in major differences in either their IL-15-induced proliferation, or their cytokine secretion response to TGF-β1. These data suggest that SMAD4 plays a redundant role in downstream TGF-β signaling in NK cells.

Original languageEnglish
Article number904
Number of pages8
JournalFrontiers in Immunology
Publication statusPublished - 1 May 2019


  • CD56bright/dim subsets
  • Hereditary Hemorrhagic Telangiectasia
  • loss-of-function mutations
  • NK cell
  • SMAD4
  • TGF-β signaling

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