Intestinal Dendritic Cells Are Altered in Number, Maturity and Chemotactic Ability in Fulminant Hepatic Failure

• Published in: PloS one Vol. 11; no. 11; p. e0166165
• Main Authors: Liu, Mei, Wang, Peng, Zhao, Min, Liu, D Y
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10-11-2016; Public Library of Science (PLoS)
• Subjects: Analysis; Animals; Antigens, CD - immunology; Antigens, CD - metabolism; Antigens, Differentiation, B-Lymphocyte - immunology; Antigens, Differentiation, B-Lymphocyte - metabolism; B7-2 Antigen - immunology; B7-2 Antigen - metabolism; Bacteria; Biology and Life Sciences; Blotting, Western; CC chemokine receptors; CCL21 protein; CCR7 protein; CCR9 protein; CD11c antigen; CD11c Antigen - immunology; CD11c Antigen - metabolism; CD83 Antigen; CD86 antigen; Cell adhesion & migration; Cell Count; Cell surface; Chemokine CCL21 - genetics; Chemokine CCL21 - immunology; Chemokine CCL21 - metabolism; Chemokines; Chemokines, CC - genetics; Chemokines, CC - immunology; Chemokines, CC - metabolism; Chemotaxis - immunology; Cytometry; D-Galactosamine; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - metabolism; Flow Cytometry; Gene expression; Gene Expression - immunology; Histocompatibility Antigens Class II - immunology; Histocompatibility Antigens Class II - metabolism; Immunoglobulins - immunology; Immunoglobulins - metabolism; Immunohistochemistry; Immunology; Intestine; Intestines - immunology; Ligands; Lipopolysaccharides; Liver; Liver diseases; Liver failure; Liver Failure, Acute - genetics; Liver Failure, Acute - immunology; Liver Failure, Acute - metabolism; Lymphatic system; Lymphocytes; Male; Markers; Maturity; Medical research; Medicine and Health Sciences; Membrane Glycoproteins - immunology; Membrane Glycoproteins - metabolism; Mice, Inbred BALB C; Mitogens; Peritonitis; Receptors, CCR - genetics; Receptors, CCR - immunology; Receptors, CCR - metabolism; Receptors, CCR7 - genetics; Receptors, CCR7 - immunology; Receptors, CCR7 - metabolism; Research and Analysis Methods; Reverse Transcriptase Polymerase Chain Reaction; RNA; Rodents; Small intestine; Spleen; Surface markers; Western blotting
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0166165

Fulminant hepatic failure (FHF) is defined as rapid acute liver injury, often complicated with spontaneous bacterial peritonitis (SBP). The precise onset of FHF with SBP is still unknown, but it is thought that SBP closely correlates with a weakened intestinal barrier. Dendritic cells (DCs) play a crucial role in forming the intestinal immune barrier, therefore the number, maturity and chemotactic ability of intestinal DCs were studied in FHF. Mouse intestinal and spleen DCs were isolated by magnetic-activated cell sorting (MACS) and surface markers of DCs, namely CD11c, CD74, CD83 and CD86, were identified using flow cytometry. Immunohistochemistry and Western blotting were performed to detect the distribution and expression of CC-chemokine receptor 7 (CCR7) and CC-chemokine receptor 9 (CCR9), as well as their ligands-CC-chemokine ligand 21 (CCL21) and CC-chemokine ligand 25 (CCL25). Real-time PCR was used to detect CCR7 and CCR9 mRNA, along with their ligands-CCL21 and CCL25 mRNA. Flow cytometry analysis showed that the markers CD74, CD83 and CD86 of CD11c+DCs were lower in the D-galactosamine (D-GalN) group and were significantly decreased in the FHF group, while there were no significant changes in the expression of these markers in the lipopolysaccharide (LPS) group. Immunohistochemistry results showed that staining for CCR7 and CCR9, as well as their ligands CCL21 and CCL25, was significantly weaker in the D-GalN and FHF groups compared with the normal saline (NS) group or the LPS group; the FHF group even showed completely unstained parts. Protein expression of CCR7 and CCR9, as well as their ligands- CCL21 and CCL25, was also lower in the D-GalN group and decreased even more significantly in the FHF group. At the gene level, CCR7 and CCR9, along with CCL21 and CCL25 mRNA expression, was lower in the D-GalN group and significantly decreased in the FHF group compared to the NS and LPS groups, consisting with the protein expression. Our study indicated that intestinal DCs were decreased in number, maturity and chemotactic ability in FHF and might contribute to a decreased function of the intestinal immune barrier in FHF.