[HTML][HTML] LEF-1 and TCF-1 orchestrate TFH differentiation by regulating differentiation circuits upstream of the transcriptional repressor Bcl6

YS Choi, JA Gullicksrud, S Xing, Z Zeng, Q Shan… - Nature …, 2015 - nature.com
YS Choi, JA Gullicksrud, S Xing, Z Zeng, Q Shan, F Li, PE Love, W Peng, HH Xue, S Crotty
Nature immunology, 2015nature.com
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 TCF-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 LEF …
Abstract
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 TCF-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 LEF-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-6Rα and gp130, enhancing expression of the costimulatory receptor ICOS and promoting expression of the transcriptional repressor Bcl6.
nature.com