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LEF-1 and TCF-1 orchestrate TFH differentiation by regulating differentiation circuits upstream of the transcriptional repressor Bcl6
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LEF-1 and TCF-1 orchestrate TFH differentiation by regulating differentiation circuits upstream of the transcriptional repressor Bcl6
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Journal Article
LEF-1 and TCF-1 orchestrate TFH differentiation by regulating differentiation circuits upstream of the transcriptional repressor Bcl6
2015
Overview
Follicular helper T cells (T
FH
cells) are specialized effector CD4
+
T cells that help B cells develop germinal centers and memory. Crotty and colleagues show that the transcription factors LEF-1 and TCF-1 are required for early T
FH
differentiation.
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.
