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Gastroenterology. 2008 Aug;135(2):529-38. doi: 10.1053/j.gastro.2008.04.020. Epub 2008 Apr 22.

Toll-like receptor signaling in small intestinal epithelium promotes B-cell recruitment and IgA production in lamina propria.

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  • 1Immunology Institute, Mount Sinai School of Medicine, New York, New York, USA.

Abstract

BACKGROUND & AIMS:

Several lines of evidence support a role for Toll-like receptor (TLR) signaling to protect the intestine from pathogenic infection. We hypothesized that TLR signaling at the level of the intestinal epithelium is critical for mucosal immune responses.

METHODS:

We generated transgenic mice that express a constitutively active form of TLR4 in the intestinal epithelium (V-TLR4 mice). Lamina propria cellularity was evaluated by immunostaining and flow cytometry. Immunoglobulin (Ig) A levels in the stool and serum were measured by enzyme-linked immunosorbent assay. Chemokine and cytokine expression were analyzed by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay.

RESULTS:

V-TLR4 transgenic mice reproduced normally and had a normal life span. Constitutive activity of TLR4 in the intestinal epithelium promoted recruitment of B cells and an increase in fecal IgA levels. Intestinal epithelial cells of V-TLR4 mice expressed higher levels of CCL20 and CCL28, chemokines known to be involved in B-cell recruitment, and of a proliferation-inducing ligand (APRIL), a cytokine that promotes T-cell-independent class switching of B cells to IgA. The changes in B-cell numbers and IgA levels were blocked by simultaneous expression in intestinal epithelial cells of M3, a herpes virus protein that binds and inhibits multiple chemokines.

CONCLUSIONS:

TLR signaling in the intestinal epithelial cells significantly elevated the production of IgA in the intestine. This effect was mediated by TLR-induced expression of a specific set of chemokines and cytokines that promoted both recruitment of B cells into the lamina propria and IgA class switching of B cells.

PMID:
18522803
PMCID:
PMC2598776
DOI:
10.1053/j.gastro.2008.04.020
[PubMed - indexed for MEDLINE]
Free PMC Article
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