Growth factor independent-1 induced by IL-4 regulates Th2 cell proliferation.
IL-4 is important in Th2 differentiation and in cell expansion. Stat6 is necessary and sufficient for both functions. Although Gata3 is critical for Th2 polarization, it is not sufficient to mediate IL-4-driven cell expansion. We report that growth factor independent-1 (Gfi-1), a Stat6-dependent transcriptional repressor, strikingly increases Th2 cell expansion by promoting proliferation and preventing apoptosis. Cells infected with a Gfi-1 retrovirus show striking enhancement of IL-2-induced Stat5 phosphorylation and repression of p27(Kip-1) expression, suggesting a potential mechanism for the Gfi-1 growth effect. The synergy of Gfi-1 and Gata3 provides a mechanism through which IL-4 could selectively promote Th2 cell expansion.
Zhu
Jinfang
J
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. jfzhu@niaid.nih.gov
Guo
Liying
L
Min
Booki
B
Watson
Cynthia J
CJ
Hu-Li
Jane
J
Young
Howard A
HA
Tsichlis
Philip N
PN
Paul
William E
WE
D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D018920:Coculture Techniques; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D050990:GATA3 Transcription Factor; D005822:Genetic Vectors; D015847:Interleukin-4 / Q000494:pharmacology*; D007700:Kinetics; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018448:Models, Immunological; D012333:RNA, Messenger / Q000096:biosynthesis; D012190:Retroviridae / Q000235:genetics; D050800:STAT6 Transcription Factor; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; C079873:Gfi1 protein, mouse; D012333:RNA, Messenger; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D015847:Interleukin-4