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Interactions among the transcription factors Runx1, RORgammat and Foxp3 regulate
the differentiation of interleukin 17-producing T cells
#MMPMID18849990
Zhang F
; Meng G
; Strober W
Nat Immunol
2008[Nov]; 9
(11
): 1297-306
PMID18849990
show ga
The molecular mechanisms underlying the differentiation of interleukin
17-producing T helper cells (T(H)-17 cells) are still poorly understood. Here we
show that optimal transcription of the gene encoding interleukin 17 (Il17)
required a 2-kilobase promoter and at least one conserved noncoding (enhancer)
sequence, CNS-5. Both cis-regulatory elements contained regions that bound the
transcription factors RORgammat and Runx1. Runx1 influenced T(H)-17
differentiation by inducing RORgammat expression and by binding to and acting
together with RORgammat during Il17 transcription. However, Runx1 also interacts
with the transcription factor Foxp3, and this interaction was necessary for the
negative effect of Foxp3 on T(H)-17 differentiation. Thus, our data support a
model in which the differential association of Runx1 with Foxp3 and with
RORgammat regulates T(H)-17 differentiation.
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