Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 276.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 276.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 276.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\27936497
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Clin+Exp+Immunol
2017 ; 187
(3
): 490-506
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Proinflammatory cytokine interferon-? and microbiome-derived metabolites dictate
epigenetic switch between forkhead box protein 3 isoforms in coeliac disease
#MMPMID27936497
Serena G
; Yan S
; Camhi S
; Patel S
; Lima RS
; Sapone A
; Leonard MM
; Mukherjee R
; Nath BJ
; Lammers KM
; Fasano A
Clin Exp Immunol
2017[Mar]; 187
(3
): 490-506
PMID27936497
show ga
Coeliac disease (CD) is an autoimmune enteropathy triggered by gluten and
characterized by a strong T helper type 1 (Th1)/Th17 immune response in the small
intestine. Regulatory T cells (T(reg) ) are CD4(+) CD25(++) forkhead box protein
3 (FoxP3(+) ) cells that regulate the immune response. Conversely to its
counterpart, FoxP3 full length (FL), the alternatively spliced isoform FoxP3 ?2,
cannot properly down-regulate the Th17-driven immune response. As the active
state of CD has been associated with impairments in T(reg) cell function, we
aimed at determining whether imbalances between FoxP3 isoforms may be associated
with the disease. Intestinal biopsies from patients with active CD showed
increased expression of FOXP3 ?2 isoform over FL, while both isoforms were
expressed similarly in non-coeliac control subjects (HC). Conversely to what we
saw in the intestine, peripheral blood mononuclear cells (PBMC) from HC subjects
did not show the same balance between isoforms. We therefore hypothesized that
the intestinal microenvironment may play a role in modulating alternative
splicing. The proinflammatory intestinal microenvironment of active patients has
been reported to be enriched in butyrate-producing bacteria, while high
concentrations of lactate have been shown to characterize the preclinical stage
of the disease. We show that the combination of interferon (IFN)-? and butyrate
triggers the balance between FoxP3 isoforms in HC subjects, while the same does
not occur in CD patients. Furthermore, we report that lactate increases both
isoforms in CD patients. Collectively, these findings highlight the importance of
the ratio between FoxP3 isoforms in CD and, for the first time, associate the
alternative splicing process mechanistically with microbial-derived metabolites.