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.
Fang
Terry C
TC
Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Yashiro-Ohtani
Yumi
Y
Del Bianco
Cristina
C
Knoblock
Dawson M
DM
Blacklow
Stephen C
SC
Pear
Warren S
WS
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