Tight junctions (TJs) are elaborate structures located on the apical region of epithelial cells that limit paracellular permeability. Tricellulin is a recently discovered TJ protein, which is concentrated at the structurally specialized tricellular TJs but also present at bicellular contacts between epithelial cells, namely in the stomach. Interestingly, several TJ proteins have been found in other than epithelial cells, as astrocytes, and tricellulin mRNA expression was reported in mature dendritic cells. These findings prompted us to look for tricellulin expression in both epithelial and immune cells in the stomach, as well as in microglia, the brain resident immunocompetent cells. Immunohistochemical analysis of human stomach tissue sections revealed peroxidase staining at three-corner contact sites, as well as at the contact between two adjacent epithelial cells, thus evidencing the expression of tricellulin not only at tricellullar but at bicellular junctions as well. Such analysis, further revealed tricellulin immunostaining in cells of the monocyte/macrophage lineage, scattered throughout the lamina propria. Cultured rat microglia exhibited a notorious tricellulin staining, consistent with an extensive expression of the protein along the cell, which was not absolutely coincident with the lysosomal marker CD68. Detection of mRNA expression by real-time PCR provided supportive evidence for the expression of the TJ protein in microglia. These data demonstrate for the first time that microglia express a TJ protein. Moreover, the expression of tricellulin both in microglia and in the stomach immune cells point to a possible role of this new TJ protein in the immune system. (C) 2011 Elsevier Inc. All rights reserved.