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Transcription factor c-Rel is indispensable for generation of thymic but not of
peripheral Foxp3(+) regulatory T cells
#MMPMID28881761
Luu M
; Jenike E
; Vachharajani N
; Visekruna A
Oncotarget
2017[Aug]; 8
(32
): 52678-52689
PMID28881761
show ga
The transcription factor c-Rel has been shown to be crucial for development of
regulatory T cells (Tregs). Recent studies have reported that the expression of
transcription factor Helios in Foxp3(+) Tregs correlates with thymic origin of
these cells (tTregs). Notably, we found that only the Helios(+)Foxp3(+) Treg cell
population was substantially reduced in c-Rel deficient mice. In contrast to a
defective tTreg development, we observed an expansion of mucosal Tregs during the
induction of acute colitis in rel(-/-) mice. Furthermore, we found a preferential
accumulation of Helios(-)Foxp3(+) Tregs in aged c-Rel deficient mice. This
unexpected finding, together with the observation that naïve CD4(+) T cells
convert into Tregs in vitro in the absence of c-Rel and presence of IL-2, provide
an evidence that extra-thymic generation of induced and peripheral Tregs (iTregs
and pTregs) is independent of c-Rel. Moreover, the treatment with IL-2/anti-IL-2
mAb (JES6-1) resulted in a widespread increase of Helios(+)Foxp3(+) Tregs in both
wild-type (WT) and rel(-/-) mice. These data suggest that exogenous IL-2
administration compensates for defective IL-2 production and reduced tTreg
numbers in c-Rel deficient mice. Our findings reveal that c-Rel is essential for
the generation of tTregs but not for that of pTregs and iTregs.
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