The GFI1–FOXO1 axis regulates NK cell maturation and function

Natural killer cells defend against malignancies and viral infections through a tightly controlled program of differentiation and maturation. However, the transcriptional mechanisms guiding this process remain incompletely defined. Using paired single-cell multiomic profiling, we identify GFI1 as an epigenetic regulator of NK cell differentiation, coordinating EOMES and T-BET transcriptional balance to promote NK cell proliferation and the transition from immature to terminally differentiated NK cell states. GFI1 represses FOXO1 chromatin accessibility in mature NK cells, which normally limits NK cell proliferation and maturation. Co-deletion of both GFI1 and FOXO1 largely rescues NK cell differentiation, identifying a critical GFI1-FOXO1 axis required for protection against tumour metastasis. These findings position GFI1 as a key transcriptional node integrating NK cell differentiation, activation and effector programs.

Authors

Institutions

Publication Details

Journal
Nature Communications
Published
2026-04-22
DOI
https://doi.org/10.1038/s41467-026-72022-6
Primary Topic
Immune Cell Function and Interaction
Type
article
Field-Weighted Citation Impact
0.00

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

The GFI1–FOXO1 axis regulates NK cell maturation and function

Zewen Kelvin Tuong, Renae Denman, Fernando Souza-Fonseca-Guimarães, Nicolas Jacquelot et al.
Nature Communications
Immune Cell Function and Interaction
article

The GFI1–FOXO1 axis regulates NK cell maturation and function

Zewen Kelvin Tuong, Renae Denman, Fernando Souza-Fonseca-Guimarães, Nicolas Jacquelot, Alexandra L. Garnham, James Dight, Gabrielle T. Belz, Huiyang Yu, M. Zeeshan Chaudhry, Qiutong Huang, Jaring Schreuder, Louisa Alim, Hiu On Man
article en

Abstract

Natural killer cells defend against malignancies and viral infections through a tightly controlled program of differentiation and maturation. However, the transcriptional mechanisms guiding this process remain incompletely defined. Using paired single-cell multiomic profiling, we identify GFI1 as an epigenetic regulator of NK cell differentiation, coordinating EOMES and T-BET transcriptional balance to promote NK cell proliferation and the transition from immature to terminally differentiated NK cell states. GFI1 represses FOXO1 chromatin accessibility in mature NK cells, which normally limits NK cell proliferation and maturation. Co-deletion of both GFI1 and FOXO1 largely rescues NK cell differentiation, identifying a critical GFI1-FOXO1 axis required for protection against tumour metastasis. These findings position GFI1 as a key transcriptional node integrating NK cell differentiation, activation and effector programs.

Nature Communications
Children's Medical Research Institute (AU), The University of Queensland (AU), The University of Melbourne (AU), Walter and Eliza Hall Institute of Medical Research (AU), Alberta Cancer Foundation (CA)
Australian Research Council, National Health and Medical Research Council
Openalex Percentile: Top 11%
Immune Cell Function and Interaction
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.