Elevated Th17 cells accompanied by decreased regulatory T cells and cytokine environment in infants with biliary atresia

Pediatr Surg Int. 2013 Dec;29(12):1249-60. doi: 10.1007/s00383-013-3421-6.

Abstract

Purpose: The aim of this study was to investigate the role of Th17 and T reg cells in biliary atresia (BA) and to assess the liver cytokine environment in BA patients.

Methods: The percentages of Th17 and T reg cells in peripheral blood mononuclear cells (PBMCs) of BA patients and healthy controls (HC) were evaluated. The serum concentrations of IL-17a and IL-23 as well as Foxp3, IL-17a, ROR-γt, IL-6, IL-1β and TGF-β1 m-RNA and protein expressions in liver tissues and the number of Foxp3, IL-17a, ROR-γt, CD4 expressing cells which infiltrated the hepatic tissues were determined.

Results: The Th17/T reg cell ratio (P < 0.001) and blood concentrations of IL-17a and IL-23 (P < 0.05) were increased in the BA as compared to the HC group. Expressions of Foxp3, ROR-γt, IL-17a, IL-1β, IL-6 as well as TGF-β1 mRNA and proteins were significantly increased in BA as compared to HC livers (P < 0.01, P < 0.05). High levels of IL-17a/ROR-γt-positive and moderate levels of Foxp3-positive cells infiltrated damaged BA bile ducts and the ratio of FoxP3+ T to CD4+ T cells was significantly lower in BA than in HC samples (P < 0.01).

Conclusion: Cytokine-induced imbalance between Th17 and T reg cells in BA livers may be involved in bile duct damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biliary Atresia / blood
  • Biliary Atresia / metabolism*
  • Blotting, Western / methods
  • Cytokines / blood
  • Cytokines / metabolism*
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Flow Cytometry / methods
  • Humans
  • Infant
  • Interleukin-17 / blood
  • Interleukin-1beta / blood
  • Interleukin-23 / blood
  • Interleukin-6 / blood
  • Leukocytes, Mononuclear / metabolism
  • Liver / metabolism
  • Male
  • Peptide Fragments / blood
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • T-Lymphocytes, Regulatory / metabolism*
  • Th17 Cells / metabolism*
  • Transforming Growth Factor beta1 / blood

Substances

  • Cytokines
  • Interleukin-17
  • Interleukin-1beta
  • Interleukin-23
  • Interleukin-6
  • Peptide Fragments
  • Transforming Growth Factor beta1
  • interleukin-1beta (163-171)