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2016 ; 7
(ä): 10789
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YY1 inhibits differentiation and function of regulatory T cells by blocking Foxp3
expression and activity
#MMPMID26892542
Hwang SS
; Jang SW
; Kim MK
; Kim LK
; Kim BS
; Kim HS
; Kim K
; Lee W
; Flavell RA
; Lee GR
Nat Commun
2016[Feb]; 7
(ä): 10789
PMID26892542
show ga
Regulatory T (T(reg)) cells are essential for maintenance of immune homeostasis.
Foxp3 is the key transcription factor for T(reg)-cell differentiation and
function; however, molecular mechanisms for its negative regulation are poorly
understood. Here we show that YY1 expression is lower in T(reg) cells than
T(conv) cells, and its overexpression causes a marked reduction of Foxp3
expression and abrogation of suppressive function of Treg cells. YY1 is increased
in T(reg) cells under inflammatory conditions with concomitant decrease of
suppressor activity in dextran sulfate-induced colitis model. YY1 inhibits
Smad3/4 binding to and chromatin remodelling of the Foxp3 locus. In addition, YY1
interrupts Foxp3-dependent target gene expression by physically interacting with
Foxp3 and by directly binding to the Foxp3 target genes. Thus, YY1 inhibits
differentiation and function of T(reg) cells by blocking Foxp3.