Biliary Epithelial Cells Are Not the Predominant Source of Hepatic CXCL12

Hepatic expression levels of CXCL12, a chemokine important in inflammatory and stem cell recruitment, and its receptor, C-X-C chemokine receptor 4, are increased during all forms of liver injury. CXCL12 is expressed by both parenchymal and nonparenchymal hepatic cells, and on the basis of immunohistochemistry, biliary epithelial cells (BECs) are thought to be a predominant source of hepatic CXCL12, thereby promoting periportal recruitment of C-X-C chemokine receptor 4–expressing lymphocytes. Our study aims to show that BECs may, in fact, not be the predominant source of hepatic CXCL12. We measured CXCL12 secretion and expression from human and murine BECs using enzyme-linked immunosorbent assay and Western blot analysis from cell culture supernatants and whole cell lysates, respectively, whereas CXCL12 expression in murine livers was analyzed in a Cxcl12-Gfp reporter mouse. Cell culture supernatants and whole cell lysates from BECs failed to demonstrate their expression of CXCL12. Furthermore, we confirmed these results with a Cxcl12-Gfp reporter mouse in which green fluorescent protein expression is notably absent from BECs. Interestingly, on the basis of green fluorescent protein expression, we demonstrate a population of CXCL12-expressing cells within the portal tract that are distinct, yet intimately associated with BECs. These findings indicate that BECs are not a predominant source of CXCL12.