Volume 2 Supplement 1

Abstracts of the 51st Workshop for Pediatric Research

Open Access

Neutralization of interleukin-17 produced by gamma delta T cells constrains inflammation in experimental biliary atresia

  • Christian Klemann1,
  • Arne Schröder1,
  • Anika Dreier1,
  • Nora Moehn1,
  • Stephanie Dippel1,
  • Thomas Winterberg1,
  • Anne Wilde1,
  • Yi Yu1,
  • Faikah Gueler2,
  • Anne Joerns3,
  • Eva Tolosa4,
  • Johannes Leonhardt5,
  • Jan D Haas6, 7,
  • Immo Prinz6,
  • Claus Petersen1 and
  • Joachim F Kuebler1
Molecular and Cellular Pediatrics20152(Suppl 1):A21

https://doi.org/10.1186/2194-7791-2-S1-A21

Published: 1 July 2015

Meeting abstract

Biliary atresia (BA) is a rare disease of the infant with unknown pathogenesis. It is characterized by inflammatory, progressive destruction of the biliary system leading to liver fibrosis and progressive deterioration of liver function. Interleukin-17a (IL-17) has been identified as a cytokine driving inflammatory and autoimmune processes. We investigated the role of IL-17 and IL-17 producing cell populations in the pathogenesis of experimental and human BA.

In the rotavirus induced BA mouse model, symptomatic animals had a significantly increased hepatic transcription of IL-17. We identified gamma delta (γδ) T cells as the exclusive source of IL-17, while classical Th17 cells were completely absent. The increased number of IL-17+ γδ T cells in BA+ animals was associated with an up-regulation of typical markers of the IL-17-axis, such as IL17a, IL17f, RORγt, CCR6 and the IL-23-receptor. In vivo, blockage of IL-17 by administration of monoclonal antibodies ameliorated the clinical course of disease, improved survival and serum bilirubin, and reduced liver inflammation.

In human infants with BA, hepatic transcription of IL-17 was significantly up-regulated compared to patients with other neonatal cholestatic diseases, while no differences in IL-17 levels were detected in patient sera.

Taken together, IL-17 released by lymphocytes bearing the γδ T cell receptor appear to be a causative factor in the inflammatory destruction of the biliary system in experimental BA. Furthermore, our data suggest an important role of the IL-17 axis in human BA. Thus, targeting the IL-17 axis could be a promising approach for therapeutic interventions.

Authors’ Affiliations

(1)
Dept. of Pediatric Surgery, Hannover Medical School
(2)
Dept. of Nephrology, Hannover Medical School
(3)
Institute of Clinical Biochemistry, Hannover Medical School
(4)
Department of Immunology, University Medical Center Hamburg-Eppendorf
(5)
Department of Pediatric Surgery, St. Bernward Hospital
(6)
Institute of Immunology, Hannover Medical School
(7)
MorphoSys AG

Copyright

© Klemann et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.