Hepatic IL-17 responses in human and murine primary biliary cirrhosis

Ruth Y Z Lan, Thucydides L. Salunga, Koichi Tsuneyama, Zhe Xiong Lian, Guo Xiang Yang, Willy Hsu, Yuki Moritoki, Aftab A. Ansari, Claudia Kemper, Jeff Price, John P. Atkinson, Ross L. Coppel, M. Eric Gershwin

Research output: Contribution to journalArticle

149 Scopus citations

Abstract

The emergence of new regulatory and pro-inflammatory immune cell subsets and cytokines dictates the need to re-examine the role of these subsets in various diseases involving the immune system. IL-17 has been recently identified as a key cytokine involved in numerous autoimmune processes. However, its role in liver autoimmune diseases remains unclear. Primary biliary cirrhosis (PBC) is characterized histologically by autoreactive CD4 and CD8 T cells surrounding damaged bile ducts. CD4+ T cells are a major source of IL-17, which compose a distinct T helper subset (Th17). Thus we set out to determine the role of IL-17 in both human and a murine model of PBC in a liver-targeted manner. Our data demonstrate an increase in the frequency of IL-17+ lymphocytic infiltration in liver tissues from PBC patients and those with other liver dysfunctions as compared to healthy livers. IL-2 receptor α knockout mice, a recently identified murine model of human PBC, also demonstrate marked aggregations of IL-17-positive cells within portal tracts and increased frequencies of Th17 cells in the liver compared to the periphery. Interestingly, CD4+ T cells from livers of normal C57BL/6J mice also secreted higher levels of IL-17 relative to those from spleens, indicating a preferential induction of Th17 cells in liver tissues. Importantly, C57BL/6J cocultures of splenic CD4+ T cells and liver non-parenchymal cells increased IL-17 production approximately 10-fold compared to T cells alone, suggesting a role of the liver microenvironment in Th17 induction in cases of liver autoimmunity and other liver inflammatory diseases.

Original languageEnglish (US)
Pages (from-to)43-51
Number of pages9
JournalJournal of Autoimmunity
Volume32
Issue number1
DOIs
StatePublished - Feb 2009

Keywords

  • CD46
  • CD T cells
  • IL-17
  • IL-2 receptor alpha
  • Liver
  • Microenvironment
  • Primary biliary cirrhosis
  • Tr1

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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  • Cite this

    Lan, R. Y. Z., Salunga, T. L., Tsuneyama, K., Lian, Z. X., Yang, G. X., Hsu, W., Moritoki, Y., Ansari, A. A., Kemper, C., Price, J., Atkinson, J. P., Coppel, R. L., & Gershwin, M. E. (2009). Hepatic IL-17 responses in human and murine primary biliary cirrhosis. Journal of Autoimmunity, 32(1), 43-51. https://doi.org/10.1016/j.jaut.2008.11.001