Notch directly regulates Gata3 expression during T helper 2 cell differentiation.
Notch signaling plays multiple roles to direct diverse decisions regarding cell fate during T cell development. During helper T (Th) cell differentiation, Notch is involved in generating optimal Th2 cell responses. Here, we present data investigating how Notch mediates Th2 cell differentiation. Notch showed a CD4(+) T cell intrinsic role in promoting IL-4 expression that required GATA-3. In the absence of Notch signals, Gata3 expression was markedly diminished. Introduction of an activated allele of Notch1 into CD4(+) T cells led to the specific and direct upregulation of a developmentally regulated Gata3 transcript that included the exon 1a sequences. Furthermore, Notch acted in parallel with GATA-3 to synergistically activate IL-4 expression. Together, these data implicate Gata3 as a direct transcriptional Notch target that acts in concert with Notch signaling to generate optimal Th2 cell responses.
Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Terry C
TC
Fang
Yumi
Y
Yashiro-Ohtani
Cristina
C
Del Bianco
Dawson M
DM
Knoblock
Stephen C
SC
Blacklow
Warren S
WS
Pear
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology; D050990:GATA3 Transcription Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D051880:Receptors, Notch / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*
D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D051880:Receptors, Notch