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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): 15677
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Ndfip1 restricts mTORC1 signalling and glycolysis in regulatory T cells to
prevent autoinflammatory disease
#MMPMID28580955
Layman AAK
; Deng G
; O'Leary CE
; Tadros S
; Thomas RM
; Dybas JM
; Moser EK
; Wells AD
; Doliba NM
; Oliver PM
Nat Commun
2017[Jun]; 8
(ä): 15677
PMID28580955
show ga
Foxp3(+) T regulatory (T(reg)) cells suppress immune cell activation and
establish normal immune homeostasis. How T(reg) cells maintain their identity is
not completely understood. Here we show that Ndfip1, a coactivator of
Nedd4-family E3 ubiquitin ligases, is required for T(reg) cell stability and
function. Ndfip1 deletion in T(reg) cells results in autoinflammatory disease.
Ndfip1-deficient T(reg) cells are highly proliferative and are more likely to
lose Foxp3 expression to become IL-4-producing T(H)2 effector cells. Proteomic
analyses indicate altered metabolic signature of Ndfip1-deficient T(reg) cells
and metabolic profiling reveals elevated glycolysis and increased mTORC1
signalling. Ndfip1 restricts T(reg) cell metabolism and IL-4 production via
distinct mechanisms, as IL-4 deficiency does not prevent hyperproliferation or
elevated mTORC1 signalling in Ndfip1-deficient T(reg) cells. Thus, Ndfip1
preserves T(reg) lineage stability and immune homeostasis by preventing the
expansion of highly proliferative and metabolically active T(reg) cells and by
preventing pathological secretion of IL-4 from T(reg) cells.
|*Signal Transduction
[MESH]
|Animals
[MESH]
|Antigen Presentation
[MESH]
|Carrier Proteins/*metabolism
[MESH]
|Cell Membrane/metabolism
[MESH]
|Cell Proliferation
[MESH]
|Female
[MESH]
|Forkhead Transcription Factors/metabolism
[MESH]
|Glycolysis
[MESH]
|Hyaluronan Receptors/metabolism
[MESH]
|Inflammation/immunology/*metabolism
[MESH]
|Intercellular Signaling Peptides and Proteins
[MESH]
|Interleukin-4/metabolism
[MESH]
|Male
[MESH]
|Mechanistic Target of Rapamycin Complex 1/*metabolism
[MESH]
free
free
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