AIM: To investigate the role of Peyer′s patch lymphocytes in the regulation of enteric epithelial barrier and ion transport function in homeostasis and host defense.METHODS: Mouse Peyer′s patch lymphocytes were cocultured with human intestinal epithelial cell line Caco-2either in the mixed or separated (isolated but permeable compartments) culture configuration. Barrier and transport functions of the Caco-2 epithelial monolayers were measured with short-circuit current (ISC) technique. Release of cytokines was measured by enzyme-linked immunosorbent assay (ELISA) and cytokine mRNA expression was analyzed by semi-quantitative RT-PCR. Barrier and iontransport functions of both culture conditions following exposure to Shigella lipopolysaccharide (LPS) were also examined.RESULTS: The transepithelial resistance (TER) of the epithelial monolayers co-cultured with Peyer′s patch lymphocytes was maintained whereas that of the Caco-2 monolayers alone significantly decreased after eight days in culture.The forskolin-induced anion secretion, in either absence or presence of LPS, was significantly suppressed in the both co-cultures as compared with the Caco-2 cells alone.Furthermore, only the mixed co-culture condition induced the expression and release of mIL-6 from Peyer′s patch lymphocytes, which could be further enhanced by LPS.However, both co-culture conditions suppressed expression and release of epithelial hIL-8 under the unstimulated conditions, while the treatment with LPS stimulated their hIL-8 expression and release.CONCLUSION: Peyer′s patch lymphocytes may modulate intestinal epithelial barrier and ion transport function in homeostasis and host defense via cell-cell contact and cytokine signaling.