Cutting edge: TGF-beta inhibits Th type 2 development through inhibition of GATA-3 expression.
TGF-beta is an important immunomodulatory cytokine that can inhibit differentiation of effector T cells. In this report, we address the molecular mechanisms through which TGF-beta inhibits differentiation of CD4(+) cells into Th type 2 cells. We demonstrate that TGF-beta inhibits GATA-3 expression in developing Th cells. We also show that inhibition of GATA-3 expression by TGF-beta is a major mechanism of inhibition of Th2 differentiation by TGF-beta as ectopic expression of GATA-3 in developing T cells overcomes the ability of TGF-beta to inhibit Th2 differentiation. TGF-beta likely inhibits GATA-3 expression at the transcriptional level and does so without interfering with IL-4 signaling.
Gorelik
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L
Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA.
Fields
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PE
Flavell
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RA
D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D050990:GATA3 Transcription Factor; D005822:Genetic Vectors / Q000276:immunology; D049452:Green Fluorescent Proteins; D006131:Growth Inhibitors / Q000502:physiology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000502:physiology; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D012190:Retroviridae / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D015534:Trans-Activators / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D014161:Transduction, Genetic; D016212:Transforming Growth Factor beta / Q000502:physiology*
D000276:Adjuvants, Immunologic; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D006131:Growth Inhibitors; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D008164:Luminescent Proteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D049452:Green Fluorescent Proteins; D015847:Interleukin-4