We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
LEF-1 and TCF-1 orchestrate T<sub>FH</sub> differentiation by regulating differentiation circuits upstream of the transcriptional repressor Bcl6.
- Authors
Choi, Youn Soo; Gullicksrud, Jodi A; Xing, Shaojun; Zeng, Zhouhao; Shan, Qiang; Li, Fengyin; Love, Paul E; Peng, Weiqun; Xue, Hai-Hui; Crotty, Shane
- Abstract
Follicular helper T cells (TFH 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 TFH cells remain incompletely understood. Here we report that selective loss of Lef1 or Tcf7 (which encode the transcription factor LEF-1 or TCF-1, respectively) resulted in TFH cell defects, while deletion of both Lef1 and Tcf7 severely impaired the differentiation of TFH cells and the formation of GCs. Forced expression of LEF-1 enhanced TFH differentiation. LEF-1 and TCF-1 coordinated such differentiation by two general mechanisms. First, they established the responsiveness of naive CD4+ T cells to TFH cell signals. Second, they promoted early TFH differentiation via the multipronged approach of sustaining expression of the cytokine receptors IL-6Rα and gp130, enhancing expression of the costimulatory receptor ICOS and promoting expression of the transcriptional repressor Bcl6.
- Subjects
T helper cells; ESTRONE; CELL differentiation; GENETIC transcription; BCL genes; CYTOKINE receptors
- Publication
Nature Immunology, 2015, Vol 16, Issue 9, p980
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni.3226