Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=27302755
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
mBio
2016 ; 7
(3
): ? Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Transcription Factor KLF2 in Dendritic Cells Downregulates Th2 Programming via
the HIF-1?/Jagged2/Notch Axis
#MMPMID27302755
Xiong Y
; Lingrel JB
; Wüthrich M
; Klein BS
; Vasudevan NT
; Jain MK
; George M
; Deepe GS Jr
mBio
2016[Jun]; 7
(3
): ? PMID27302755
show ga
The adaptive immune response is tightly regulated by complex signals in dendritic
cells (DCs). Although Th2 polarization is dictated by defined functional DC
subsets, the molecular factors that govern the amplitude of these responses are
not well understood. Krüppel-like factor 2 (KLF2) is a transcription factor that
negatively regulates the activation of numerous immune cells in response to
stimuli. Here, we demonstrate that suppression of KLF2 in conditioned DCs
preferentially amplifies Th2 responses in two model systems, one of which is a
prototypical intracellular pathogen and the other an allergen. This elevation in
Th2 responses was dependent on contact-mediated Notch signaling in vitro and in
vivo A deficiency of KLF2 increased the expression of Notch ligand Jagged2 via
hypoxia-inducible factor 1? (HIF-1?), which led to Th2 amplification. Our results
revealed a novel circuit in DCs for Th2 polarization that is governed by KLF2.
IMPORTANCE: Dendritic cells are the key element that bridges innate and adaptive
immunity. A complex and not-well-understood area in dendritic cell biology is the
regulatory network that predetermines or moderates their function to shape the
adaptive immune response. Our study for the first time demonstrates that KLF2, a
transcription factor, conditions dendritic cells to regulate Th2 responses via a
Jagged2/Notch axis. Downregulation of KLF2 expression in dendritic cells may
provide a beneficial effect for treatment of diseases such as obesity or
parasitic infections but may be deleterious in the case of invasion by
intracellular pathogens. Strategies to tune KLF2 may be useful for future
therapeutic approaches to particular diseases of mankind.
free
free
free
