Open AccessCD 137 signaling enhances tight junction resistance in intestinal epithelial cells
Author(s) -
Gusti Veronica,
Bennett Kaila M.,
Lo David D.
Publication year - 2014
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.12090
Subject(s) - microbiology and biotechnology , transfection , cd137 , chemistry , signal transduction , cytokine , tumor necrosis factor alpha , biology , cell culture , t cell , immunology , immune system , genetics
Abstract Treatment of Caco‐2‐ BB e intestinal epithelial cells ( BB e) with TNF ‐ α and lymphotoxin‐ β ( LT ‐ β ) receptor agonists induced the expression of the TNF receptor superfamily gene TNFRSF 9/ CD 137 . In the gut, these cytokines are known to be involved in both inflammatory responses and development of organized lymphoid tissues; thus, it was notable that in CD 137 ‐deficient mice Peyer's patch M cells lacked transcytosis function. To examine the direct effect of CD 137 expression on epithelial cell function independent of other cytokine effects including CD 137L triggering, we stably transfected BB e cells to express CD 137. CD 137 was found at the cell surface as well as the cytoplasm, and confocal microscopy suggested that aggregates of CD 137 at the lateral and basolateral surface may be associated with cytoplasmic actin filament termini. Many of the CD 137 clusters were colocalized with extracellular fibronectin providing a possible alternative ligand for CD 137. Interestingly, we found that CD 137‐expressing cells showed significantly higher transepithelial electrical resistance ( TEER ) accompanied by an increase in claudin‐4 and decrease in claudin‐3 protein expression. By contrast, transfection with a truncated CD 137 lacking the cytoplasmic signaling domain did not affect TEER . Finally, CD 137‐deficient mice showed increased intestinal permeability upon dextran sodium sulfate ( DSS ) treatment as compared to control mice. Our results suggest that cytokine‐induced expression of CD 137 may be important in enhancing epithelial barrier function in the presence of intestinal inflammation as well as influencing cytoskeletal organization.