Journal of Clinical Immunology

, Volume 32, Issue 3, pp 611–621 | Cite as

The Role of Innate Cells Is Coupled to a Th1-Polarized Immune Response in Pediatric Nonalcoholic Steatohepatitis

  • Nazarena E. Ferreyra Solari
  • María Eugenia Inzaugarat
  • Placida Baz
  • Elena De Matteo
  • Carol Lezama
  • Marcela Galoppo
  • Cristina Galoppo
  • Alejandra C. Cherñavsky
Article

Abstract

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.

Keywords

Memory and naive T cell subsets polymorphonuclear cells oxidative stress Th1/Th2 cytokines pediatric NASH 

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Nazarena E. Ferreyra Solari
    • 1
  • María Eugenia Inzaugarat
    • 1
  • Placida Baz
    • 1
  • Elena De Matteo
    • 2
  • Carol Lezama
    • 3
  • Marcela Galoppo
    • 3
  • Cristina Galoppo
    • 3
  • Alejandra C. Cherñavsky
    • 1
  1. 1.Laboratorio de InmunogenéticaHospital de Clínicas “José de San Martín”, Universidad de Buenos AiresBuenos AiresArgentina
  2. 2.Servicio de PatologíaHospital de Niños “Dr. R. Gutierrez”, Universidad de Buenos AiresBuenos AiresArgentina
  3. 3.Unidad de HepatologíaHospital de Niños “Dr. Ricardo Gutiérrez”, Universidad de Buenos AiresBuenos AiresArgentina

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