Journal
GASTROENTEROLOGY
Volume 135, Issue 2, Pages 529-538Publisher
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1053/j.gastro.2008.04.020
Keywords
-
Categories
Funding
- NCI NIH HHS [R01 CA161373] Funding Source: Medline
- NIAID NIH HHS [R21 AI052266, R56 AI052266, AI052266, R01 AI052266] Funding Source: Medline
- NIDDK NIH HHS [P01 DK072201-029001, DK069594, R21 DK069594, R01 DK067989, P01 DK072201, P01 DK072201-01A10002] Funding Source: Medline
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available