Related Experiment Video
Updated: Jul 2, 2026

In Vitro Differentiation of Mouse Granulocyte-macrophage-colony-stimulating Factor (GM-CSF)-producing T Helper (THGM) Cells
Published on: September 10, 2018
Gfi1-mediated stabilization of GATA3 protein is required for Th2 cell differentiation
Ryo Shinnakasu1, Masakatsu Yamashita, Makoto Kuwahara
1Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba 260-8670, Japan.
Abstract:
The differentiation of naive CD4 T cells into Th2 cells requires the T cell receptor-mediated activation of the ERK MAPK cascade. Little is known, however, in regard to how the ERK MAPK cascade regulates Th2 cell differentiation. We herein identified Gfi1 (growth factor independent-1) as a downstream target of the ERK MAPK cascade for Th2 cell differentiation. In the absence of Gfi1, interleukin-5 production and the change of histone modification at the interleukin-5 gene locus were severely impaired. Furthermore, the interferon gamma gene showed a striking activation in the Gfi1(-/-) Th2 cells. An enhanced ubiquitin/proteasome-dependent degradation of GATA3 protein was observed in Gfi1(-/-) Th2 cells, and the overexpression of GATA3 eliminated the defect of Th2 cell function in Gfi1-deficient Th2 cells. These data suggest that the T cell receptor-mediated induction of Gfi1 controls Th2 cell differentiation through the regulation of GATA3 protein stability.
Related Concept Videos
TGF - β Signaling Pathway
Activation and Inactivation of G Proteins
GTPases and their Regulation
Large G-proteins, also known...
Master Transcription Regulators
Small GTPases - Ras and Rho
Three regulatory proteins control their activity:
General Transcription Factors
