The Runx3 transcription factor augments Th1 and down-modulates Th2 phenotypes by interacting with and attenuating GATA3.
Recently, it was reported that the expression of Runt-related transcription factor 3 (Runx3) is up-regulated in CD4(+) helper T cells during Th1 cell differentiation, and that Runx3 functions in a positive feed-forward manner with the T-box family transcription factor, T-bet, which is a master regulator of Th1 cell differentiation. The relative expression levels of IFN-gamma and IL-4 are also regulated by the Th2-associated transcription factor, GATA3. Here, we demonstrate that Runx3 was induced in Th2 as well as Th1 cells and that Runx3 interacted with GATA3 and attenuated GATA3 transcriptional activity. Ectopic expression of Runx3 in vitro in cultured cells or transgenic expression of Runx3 in mice accelerated CD4(+) cells to a Th1-biased population or down-modulated Th2 responses, in part by neutralizing GATA3. Our results suggest that the balance of Runx3 and GATA3 is one factor that influences the manifestation of CD4(+) cells as the Th1 or Th2 phenotypes.
Kohu
Kazuyoshi
K
Institute of Development, Aging and Cancer, Graduate School of Life Sciences, Tohoku University, Sendai, Japan.
Ohmori
Hidetaka
H
Wong
Won Fen
WF
Onda
Daisuke
D
Wakoh
Takeshi
T
Kon
Shunsuke
S
Yamashita
Masakatsu
M
Nakayama
Toshinori
T
Kubo
Masato
M
Satake
Masanobu
M
D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000502:physiology; D000818:Animals; D002450:Cell Communication / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D050677:Core Binding Factor Alpha 3 Subunit / Q000378:metabolism / Q000502:physiology*; D015536:Down-Regulation / Q000276:immunology*; D050990:GATA3 Transcription Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D016130:Immunophenotyping; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D050677:Core Binding Factor Alpha 3 Subunit; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; C493730:Runx3 protein, mouse