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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 PLoS+One
2016 ; 11
(3
): e0150968
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Preferential Secretion of Thymic Stromal Lymphopoietin (TSLP) by Terminally
Differentiated Esophageal Epithelial Cells: Relevance to Eosinophilic Esophagitis
(EoE)
#MMPMID26992000
Chandramouleeswaran PM
; Shen D
; Lee AJ
; Benitez A
; Dods K
; Gambanga F
; Wilkins BJ
; Merves J
; Noah Y
; Toltzis S
; Yearley JH
; Spergel JM
; Nakagawa H
; Malefyt Rd
; Muir AB
; Wang ML
PLoS One
2016[]; 11
(3
): e0150968
PMID26992000
show ga
Eosinophilic esophagitis (EoE) is a chronic Th2 and food antigen-mediated disease
characterized by esophageal eosinophilic infiltration. Thymic stromal
lymphopoetin (TSLP), an epithelial derived cytokine which bridges innate and
Th2-type adaptive immune responses in other allergic conditions, is overexpressed
in esophageal biopsies of EoE subjects. However, the triggers of TSLP expression
in the esophageal epithelium are unknown. The objective of the current study was
to characterize TSLP expression in human esophageal epithelium in EoE in vivo and
to determine the role of food antigens upon epithelial TSLP expression in vitro.
Using immunohistochemistry (IHC), we localized TSLP in esophageal biopsies of
active EoE (?15 eos/hpf), inactive EoE (<15 eos/hpf) and non-EoE control
subjects, and found that TSLP expression was restricted to the differentiated
suprabasal layer of the epithelium in actively inflamed EoE biopsies. Consistent
with these results in vivo, inducible TSLP protein secretion was higher in CaCl2
differentiated telomerase-immortalized esophageal epithelial cells (EPC2-hTERT)
compared to undifferentiated cells of the basal phenotype, following stimulation
with the TLR3 ligand poly(I:C). To determine whether food antigens could directly
induce epithelial TSLP secretion, differentiated and undifferentiated primary
esophageal epithelial cells from EoE and non-EoE subjects were challenged with
food antigens clinically relevant to EoE: Chicken egg ovalbumin (OVA), wheat, and
milk proteins beta-lactoglobulin (blg) and beta-casein. Food antigens failed to
induce TSLP secretion by undifferentiated cells; in contrast, only OVA induced
TSLP secretion in differentiated epithelial cells from both EoE and control cell
lines, an effect abolished by budesonide and NF-?b inhibition. Together, our
study shows that specific food antigens can trigger innate immune mediated
esophageal TSLP secretion, suggesting that esophageal epithelial cells at the
barrier surface may play a significant role in the pathogenesis of EoE by
regulating TSLP expression.