Loss-of-Function in SMAD4 Might Not Be Critical for Human Natural Killer Cell Responsiveness to TGF-beta
Lachlan P Healy, Gustavo P Rossi, Jai Rautela, Charlotte A Slade, Nicholas D Huntington, Ingrid M Winship, Fernando Souza-Fonseca-Guimaraes
Frontiers in Immunology | FRONTIERS MEDIA SA | Published : 2019
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.
Awarded by National Health and Medical Research Council (NHMRC) of Australia
Awarded by NHMRC Early Career Fellowship
Awarded by National Breast Cancer Foundation (NBCF) Fellowship
Awarded by Priority-driven Collaborative Cancer Research Scheme
Awarded by NHMRC postgraduate scholarship
Awarded by Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior postgraduate scholarship
This work is supported by project grants from the National Health and Medical Research Council (NHMRC) of Australia (#1124784, #1066770, #1057852, #1124907 to NH; and #1140406 to FS-F-G). FS-F-G. was supported by a NHMRC Early Career Fellowship (1088703), a National Breast Cancer Foundation (NBCF) Fellowship (PF-15-008), a grant #1120725 awarded through the Priority-driven Collaborative Cancer Research Scheme and funded by Cure Cancer Australia with the assistance of Cancer Australia. NH is a NHMRC CDF2 Fellow (1124788), a recipient of a Melanoma Research Grant from the Harry J Lloyd Charitable Trust, Melanoma Research Alliance Young Investigator Award, Ian Potter Foundation equipment grant and a CLIP grant from Cancer Research Institute. This study was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC Independent Research Institute Infrastructure Support scheme. LH is supported by a Matty's Soldiers MPhil scholarship. CS was supported by an NHMRC postgraduate scholarship (1075666). GR was supported by a Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior postgraduate scholarship (PDSE-88881.188501/2018-01).