info:eu-repo/semantics/article
The role of innate cells is coupled to a Th1-polarized immune response in pediatric nonalcoholic steatohepatitis
Fecha
2012-01Registro en:
Ferreyra Solari, Nazarena Eugenia; Inzaugarat, Maria Eugenia; Baz, Placida; de Matteo, Elena Noemí; Lezama, Carol; et al.; The role of innate cells is coupled to a Th1-polarized immune response in pediatric nonalcoholic steatohepatitis; Springer/Plenum Publishers; Journal of Clinical Immunology; 32; 3; 1-2012; 611-621
0271-9142
CONICET Digital
CONICET
Autor
Ferreyra Solari, Nazarena Eugenia
Inzaugarat, Maria Eugenia
Baz, Placida
de Matteo, Elena Noemí
Lezama, Carol
Galoppo, Marcela
Galoppo, María Cristina
Cherñavsky, Alejandra Claudia
Resumen
Background: Nonalcoholic steatohepatitis (NASH) is a chronic inflammatory liver disease influenced by risk factors for the metabolic syndrome. In adult patients, NASH is associated with an altered phenotype and functionality of peripheral immune cells, the recruitment of leukocytes and intrahepatic activation, and an exacerbated production of reactive oxygen species (ROS) and cytokines. It remains unclear if the previously described differences between pediatric and adult nonalcoholic fatty liver diseases also reflect differences in their pathogenesis. Aims: We aimed to investigate the phenotype and functionality of circulating immune cells and the potential contribution of liver infiltrating leukocytes to the immunological imbalance in pediatric NASH. Results: By a real-time PCR-based analysis of cytokines and immunohistochemical staining of liver biopsies, we demonstrated that the hepatic microenvironment is dominated by interferon-gamma (IFN-γ) but not interleukin-4 and is infiltrated by a higher number of CD8 + cells in pediatric NASH. The number of infiltrating neutrophils positively correlated with ROS generation by peripheral polymorphonuclear cells. By a flow cytometric analysis of peripheral blood lymphocytes, a distinctive increase in CD8 + CD45RO and CD8 + CD45RA subpopulations and an increased production of IFN-γ by CD4 + and CD8 + cells were shown. The production of ROS following PMA stimulation was augmented in circulating neutrophils but not in monocytes. Conclusion: In sum, the distinctive phenotype and functionality of infiltrating and circulating cells suggest that the role of innate cells is coupled to a Th1-polarized immune response in pediatric NASH.