CD137 signaling enhances tight junction resistance in intestinal epithelial cells
| Autor: | Kaila M. Bennett, Veronica Gusti, David Lo |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Physiology
tight junction medicine.medical_treatment Biology digestive system Epithelium 03 medical and health sciences 0302 clinical medicine lymphotoxin Physiology (medical) medicine mucosal barrier Original Research 030304 developmental biology Microfold cell 0303 health sciences Tight junction CD137 Transfection Cell biology Fibronectin Cytokine Transcytosis Cytoplasm Immunology biology.protein 030215 immunology |
| Zdroj: | Physiological Reports |
| ISSN: | 2051-817X |
| Popis: | Treatment of Caco‐2‐BBe intestinal epithelial cells (BBe) with TNF‐α and lymphotoxin‐β (LT‐β) receptor agonists induced the expression of the TNF receptor superfamily gene TNFRSF9/CD137. 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 CD137‐deficient mice Peyer's patch M cells lacked transcytosis function. To examine the direct effect of CD137 expression on epithelial cell function independent of other cytokine effects including CD137L triggering, we stably transfected BBe cells to express CD137. CD137 was found at the cell surface as well as the cytoplasm, and confocal microscopy suggested that aggregates of CD137 at the lateral and basolateral surface may be associated with cytoplasmic actin filament termini. Many of the CD137 clusters were colocalized with extracellular fibronectin providing a possible alternative ligand for CD137. Interestingly, we found that CD137‐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 CD137 lacking the cytoplasmic signaling domain did not affect TEER. Finally, CD137‐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 CD137 may be important in enhancing epithelial barrier function in the presence of intestinal inflammation as well as influencing cytoskeletal organization. CD137 expression induced in intestinal epithelial cells by inflammatory cytokines causes an increase in transepithelial electrical resistance, in part, by increasing Claudin 4 expression. This may play a role in helping maintain barrier function during intestinal inflammation. |
| Databáze: | OpenAIRE |
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