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2017 ; 10
(2
): 373-384
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An LGG-derived protein promotes IgA production through upregulation of APRIL
expression in intestinal epithelial cells
#MMPMID27353252
Wang Y
; Liu L
; Moore DJ
; Shen X
; Peek RM
; Acra SA
; Li H
; Ren X
; Polk DB
; Yan F
Mucosal Immunol
2017[Mar]; 10
(2
): 373-384
PMID27353252
show ga
p40, a Lactobacillus rhamnosus GG (LGG)-derived protein, transactivates epidermal
growth factor receptor (EGFR) in intestinal epithelial cells, leading to
amelioration of intestinal injury and inflammation. To elucidate mechanisms by
which p40 regulates mucosal immunity to prevent inflammation, this study aimed to
determine the effects and mechanisms of p40 on regulation of a
proliferation-inducing ligand (APRIL) expression in intestinal epithelial cells
for promoting immunoglobulin A (IgA) production. p40 upregulated April gene
expression and protein production in mouse small intestine epithelial (MSIE)
cells, which were inhibited by blocking EGFR expression and kinase activity.
Enteroids from Egfr(fl/fl), but not Egfr(fl/fl)-Vil-Cre mice with EGFR
specifically deleted in intestinal epithelial cells, exhibited increased April
gene expression by p40 treatment. p40-conditioned media from MSIE cells increased
B-cell class switching to IgA(+) cells and IgA production, which was suppressed
by APRIL receptor-neutralizing antibodies. Treatment of B cells with p40 did not
show any effects on IgA production. p40 treatment increased April gene expression
and protein production in small intestinal epithelial cells, fecal IgA levels,
IgA(+)B220(+), IgA(+)CD19(+), and IgA(+) plasma cells in lamina propria of
Egfr(fl/fl), but not of Egfr(fl/fl)-Vil-Cre, mice. Thus p40 upregulates
EGFR-dependent APRIL production in intestinal epithelial cells, which may
contribute to promoting IgA production.
|*Antibody Formation
[MESH]
|Animals
[MESH]
|B-Lymphocytes/*immunology
[MESH]
|Bacterial Proteins/immunology/*metabolism
[MESH]
|Cells, Cultured
[MESH]
|Epithelial Cells/*immunology
[MESH]
|ErbB Receptors/genetics/metabolism
[MESH]
|Immunoglobulin A/metabolism
[MESH]
|Intestine, Small/*pathology
[MESH]
|Lacticaseibacillus rhamnosus/*immunology
[MESH]
|Mice
[MESH]
|Mice, Inbred C57BL
[MESH]
|Mice, Knockout
[MESH]
|Mice, Transgenic
[MESH]
|RNA, Small Interfering/genetics
[MESH]
|Transcriptional Activation
[MESH]
|Tumor Necrosis Factor Ligand Superfamily Member 13/genetics/*metabolism
[MESH]