GATA-3 suppresses Th1 development by downregulation of Stat4 and not through effects on IL-12Rbeta2 chain or T-bet

Takashi Usui; Ryuta Nishikomori; Atsushi Kitani; Warren Strober

doi:10.1016/s1074-7613(03)00057-8

GATA-3 suppresses Th1 development by downregulation of Stat4 and not through effects on IL-12Rbeta2 chain or T-bet

Immunity. 2003 Mar;18(3):415-28. doi: 10.1016/s1074-7613(03)00057-8.

Authors

Takashi Usui¹, Ryuta Nishikomori, Atsushi Kitani, Warren Strober

Affiliation

¹ Mucosal Immunity Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA. wstrober@niaid.nih.gov

PMID: 12648458
DOI: 10.1016/s1074-7613(03)00057-8

Abstract

To further understand the interaction among GATA-3, Stat4, and T-bet in helper T cell development, we first showed that retroviral expression of GATA-3 in developing Th1 cells suppresses Th1 development through downregulation of Stat4 rather through downregulation of the IL-12Rbeta2 chain. Correspondingly, Stat4 levels are greatly suppressed during physiological Th2 development. Then, using cells doubly infected with GFP- and YFP-expressing retroviruses, we showed that retroviral GATA-3 expression in developing Th1 cells does not block Th1 development in cells coexpressing Stat4 but does so in cells coexpressing T-bet. Finally, we showed that retroviral Stat4 expression could facilitate Th2-->Th1 conversion in cells bearing an IL-12Rbeta2 transgene, even in cells lacking T-bet. These findings reassert that Stat4 signaling is a central element of Th1/Th2 development.

MeSH terms

Animals
Cell Differentiation
DNA-Binding Proteins / genetics*
DNA-Binding Proteins / immunology*
DNA-Binding Proteins / metabolism
Down-Regulation
GATA3 Transcription Factor
Gene Expression
Interferon-gamma / biosynthesis
Interleukin-13 / metabolism
Interleukin-4 / metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
RNA, Messenger / genetics
RNA, Messenger / metabolism
Receptors, Interleukin / genetics
Receptors, Interleukin-12
Retroviridae / genetics
STAT4 Transcription Factor
T-Box Domain Proteins
Th1 Cells / cytology
Th1 Cells / immunology*
Th1 Cells / metabolism
Th2 Cells / cytology
Th2 Cells / immunology
Th2 Cells / metabolism
Trans-Activators / genetics*
Trans-Activators / immunology*
Trans-Activators / metabolism
Transcription Factors / genetics

Substances

DNA-Binding Proteins
GATA3 Transcription Factor
Gata3 protein, mouse
Interleukin-13
RNA, Messenger
Receptors, Interleukin
Receptors, Interleukin-12
STAT4 Transcription Factor
Stat4 protein, mouse
T-Box Domain Proteins
T-box transcription factor TBX21
Trans-Activators
Transcription Factors
Interleukin-4
Interferon-gamma