THE ROLE OF BILE DUCT EPITHELIA AS ANTIGEN PRESENTING CELLS IN THE MURINE MODEL OF BILIARY ATRESIA

Background: The bile duct injury found in patients with biliary atresia (BA) is associated with a lymphocytic and monocytic inflammatory response with localized production of Th1 cytokines. Immunohistochemistry studies have shown that cholangiocytes express surface markers found on antigen presenting cells (APCs) including MHC class II and co-stimulatory molecules (CD80, CD86, CD40). Furthermore, Lazaridis et al have described a "reactive cholangiocyte phenotype" found in cholangiopathies including BA, where cholangiocytes are capable of expressing APC surface markers and producing various cytokines. Hypothesis: Cholangiocytes in BA are competent APCs, contributing to persistent T-cell mediated inflammation and bile duct injury. To test this hypothesis, the Rhesus rotavirus (RRV)-induced murine model of BA was utilized. Methods: Cholangiocyte surface expression of APC molecules was performed by FACS analysis on both a murine cholangiocyte cell line and cholangiocytes isolated ex vivo from normal mouse livers. Additional FACS analysis to determine changes in APC marker expression was performed on cholangiocytes subjected to RRV infection or co-cultured with Th1 cytokines. Results: APC surface markers (MHC classes I & II, CD40, CD80, CD86) were present on murine cholangiocytes. RRV infection of the cholangiocyte cell line increased expression of MHC II, CD80, and CD40 and co-culture with cytokines markedly increased expression of MHC I, and minimally increased expression of CD80 and CD86. Conclusions: Murine cholangiocytes possess the key surface markers necessary for antigen presentation. RRV infection and co-culture with cytokines increased APC marker expression. Future experiments will focus on the functional ability of cholangiocytes to present antigen and the role of cholangiocytes as effector cells capable of inflammatory cytokine production.