Notch directly regulates Gata3 expression during T helper 2 cell differentiation

被引:326
作者
Fang, Terry C.
Yashiro-Ohtani, Yumi
Del Bianco, Cristina
Knoblock, Dawson M.
Blacklow, Stephen C.
Pear, Warren S. [1 ]
机构
[1] Univ Penn, Inst Med & Engn, Dept Pathol & Lab Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA
[2] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA
关键词
D O I
10.1016/j.immuni.2007.04.018
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 Notchl 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.
引用
收藏
页码:100 / 110
页数:11
相关论文
共 52 条
[11]   The cell type-specific expression of the murine IL-13 gene is regulated by GATA-3 [J].
Kishikawa, H ;
Sun, J ;
Choi, A ;
Miaw, SC ;
Ho, IC .
JOURNAL OF IMMUNOLOGY, 2001, 167 (08) :4414-4420
[12]   Ectopic expression of activated Stat6 induces the expression of Th2-specific cytokines and transcription factors in developing Th1 cells [J].
Kurata, H ;
Lee, HJ ;
O'Garra, A ;
Arai, N .
IMMUNITY, 1999, 11 (06) :677-688
[13]  
Lee CY, 2001, J SCHED, V4, P3, DOI 10.1002/1099-1425(200101/02)4:1<3::AID-JOS57>3.0.CO
[14]  
2-D
[15]   Th2 lineage commitment and efficient IL-4 production involves extended demethylation of the IL-4 gene [J].
Lee, DU ;
Agarwal, S ;
Rao, A .
IMMUNITY, 2002, 16 (05) :649-660
[16]   GATA-3 induces T helper cell type 2 (Th2) cytokine expression and chromatin remodeling in committed Th1 cells [J].
Lee, HJ ;
Takemoto, N ;
Kurata, H ;
Kamogawa, Y ;
Miyatake, S ;
O'Garra, A ;
Arai, N .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (01) :105-115
[17]   Temporal and spatial control of murine GATA-3 transcription by promoter-proximal regulatory elements [J].
Lieuw, KH ;
Li, GL ;
Zhou, YH ;
Grosveld, F ;
Engel, JD .
DEVELOPMENTAL BIOLOGY, 1997, 188 (01) :1-16
[18]   Delta1-Notch3 interactions bias the functional differentiation of activated CD4+ T cells [J].
Maekawa, Y ;
Tsukumo, S ;
Chiba, S ;
Hirai, H ;
Hayashi, Y ;
Okada, H ;
Kishihara, K ;
Yasutomo, K .
IMMUNITY, 2003, 19 (04) :549-559
[19]   Regulation of lymphoid development, differentiation, and function by the notch pathway [J].
Maillard, I ;
Fang, T ;
Pear, WS .
ANNUAL REVIEW OF IMMUNOLOGY, 2005, 23 :945-974
[20]   Mastermind critically regulates Notch-mediated lymphoid cell fate decisions [J].
Maillard, I ;
Weng, AP ;
Carpenter, AC ;
Rodriguez, CG ;
Sai, H ;
Xu, LW ;
Allman, D ;
Aster, JC ;
Pear, WS .
BLOOD, 2004, 104 (06) :1696-1702