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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Nat+Commun
2017 ; 8
(ä): 15876
Nephropedia Template TP
Wu D
; Luo Y
; Guo W
; Niu Q
; Xue T
; Yang F
; Sun X
; Chen S
; Liu Y
; Liu J
; Sun Z
; Zhao C
; Huang H
; Liao F
; Han Z
; Zhou D
; Yang Y
; Xu G
; Cheng T
; Feng X
Nat Commun
2017[Jun]; 8
(ä): 15876
PMID28621313
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Regulatory T (T(reg)) cells are a distinct T-cell lineage characterized by
sustained Foxp3 expression and potent suppressor function, but the upstream
dominant factors that preserve T(reg) lineage-specific features are mostly
unknown. Here, we show that Lkb1 maintains T(reg) cell lineage identity by
stabilizing Foxp3 expression and enforcing suppressor function. Upon T-cell
receptor (TCR) stimulation Lkb1 protein expression is upregulated in T(reg) cells
but not in conventional T cells. Mice with T(reg) cell-specific deletion of Lkb1
develop a fatal early-onset autoimmune disease, with no Foxp3 expression in most
T(reg) cells. Lkb1 stabilizes Foxp3 expression by preventing STAT4-mediated
methylation of the conserved noncoding sequence 2 (CNS2) in the Foxp3 locus.
Independent of maintaining Foxp3 expression, Lkb1 programs the expression of a
wide spectrum of immunosuppressive genes, through mechanisms involving the
augmentation of TGF-? signalling. These findings identify a critical function of
Lkb1 in maintaining T(reg) cell lineage identity.
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