BACKGROUND/AIMS: To clarify the primary biliary cirrhosis (PBC)-specific antigen-presenting mechanism, we examined the distribution and phenotypic characteristics of infiltrating dendritic cells (DCs) with respect to bile ducts and the mechanism of migration in terms of the periductal cytokine milieu and biliary innate immunity. METHODS AND RESULTS: Immunohistochemistry using liver sections from patients with PBC and controls revealed that blood dendritic cell antigen (BDCA)-2(+) plasmacytoid DCs were found mainly in the portal tracts in PBC and the controls, but their distribution was not related to bile ducts. BDCA-1(+) and CD19(-) myeloid DCs were also found in portal tracts in PBC and the controls and, in particular, Langerin+Langerhans cells (LCs) were dominantly scattered around or within biliary epithelial layers of the damaged bile ducts in PBC. Moreover, experiments with cultured human biliary epithelial cells (BECs) showed that an LC-attracting chemokine, macrophage inflammatory protein-3α, was produced by BECs in the response to cytokines [interleukin (IL)-1β, tumour necrosis factor-α and IL-17] and pathogen-associated molecular patterns. CONCLUSIONS: LCs existing around or within biliary epithelial layers are important as periductal antigen-presenting cells in PBC and the migration of LCs into bile ducts is closely associated with the periductal cytokine milieu and biliary innate immunity in PBC.
BACKGROUND/AIMS: To clarify the primary biliary cirrhosis (PBC)-specific antigen-presenting mechanism, we examined the distribution and phenotypic characteristics of infiltrating dendritic cells (DCs) with respect to bile ducts and the mechanism of migration in terms of the periductal cytokine milieu and biliary innate immunity. METHODS AND RESULTS: Immunohistochemistry using liver sections from patients with PBC and controls revealed that blood dendritic cell antigen (BDCA)-2(+) plasmacytoid DCs were found mainly in the portal tracts in PBC and the controls, but their distribution was not related to bile ducts. BDCA-1(+) and CD19(-) myeloid DCs were also found in portal tracts in PBC and the controls and, in particular, Langerin+Langerhans cells (LCs) were dominantly scattered around or within biliary epithelial layers of the damaged bile ducts in PBC. Moreover, experiments with cultured human biliary epithelial cells (BECs) showed that an LC-attracting chemokine, macrophage inflammatory protein-3α, was produced by BECs in the response to cytokines [interleukin (IL)-1β, tumour necrosis factor-α and IL-17] and pathogen-associated molecular patterns. CONCLUSIONS: LCs existing around or within biliary epithelial layers are important as periductal antigen-presenting cells in PBC and the migration of LCs into bile ducts is closely associated with the periductal cytokine milieu and biliary innate immunity in PBC.
Authors: Daniel S Smyk; Eirini I Rigopoulou; Albert Pares; Charalambos Billinis; Andrew K Burroughs; Luigi Muratori; Pietro Invernizzi; Dimitrios P Bogdanos Journal: Clin Dev Immunol Date: 2012-05-30