LEF-1 and TCF-1 orchestrate TFH differentiation by regulating differentiation circuits upstream of the transcriptional repressor BcI6

被引:262
作者
Choi, Youn Soo [1 ]
Gullicksrud, Jodi A. [2 ,3 ]
Xing, Shaojun [2 ]
Zeng, Zhouhao [4 ]
Shan, Qiang [2 ]
Li, Fengyin [2 ]
Love, Paul E. [5 ]
Peng, Weiqun [4 ]
Xue, Hai-Hui [2 ,3 ]
Crotty, Shane [1 ]
机构
[1] La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA USA
[2] Univ Iowa, Dept Microbiol, Iowa City, IA 52242 USA
[3] Univ Iowa, Carver Coll Med, Interdisciplinary Immunol Grad Program, Iowa City, IA USA
[4] George Washington Univ, Dept Phys, Washington, DC 20052 USA
[5] NICHD, Sect Cellular & Dev Biol, NIH, Bethesda, MD USA
基金
美国国家卫生研究院;
关键词
FOLLICULAR HELPER-CELL; B-CELLS; ICOS; BCL6; CD4(+); GENERATION; T-HELPER-1; FATE; INDUCTION; PROMOTE;
D O I
10.1038/ni.3226
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Follicular helper T cells (T-FH cells) are specialized effector CD4(+) T cells that help B cells develop germinal centers (GCs) and memory. However, the transcription factors that regulate the differentiation of T-FH cells remain incompletely understood. Here we report that selective loss of Lef1 or Tcf7 (which encode the transcription factor LEF-1 or ICE-1, respectively) resulted in T-FH cell defects, while deletion of both Lef1 and Tcf7 severely impaired the differentiation of T-FH cells and the formation of GCs. Forced expression of LEE-1 enhanced T-FH differentiation. LEF-1 and TCF-1 coordinated such differentiation by two general mechanisms. First, they established the responsiveness of naive CD4(+) T cells to T-FH cell signals. Second, they promoted early T-FH differentiation via the multipronged approach of sustaining expression of the cytokine receptors IL-61R alpha and gp130, enhancing expression of the costimulatory receptor ICOS and promoting expression of the transcriptional repressor BcI6.
引用
收藏
页码:980 / 990
页数:11
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