Periductal interleukin-17 production in association with biliary innate immunity contributes to the pathogenesis of cholangiopathy in primary biliary cirrhosis

K. Harada, Shinji Shimoda, Y. Sato, K. Isse, H. Ikeda, Y. Nakanuma

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Abstract

An innate immune response to bacterial components is speculated to be involved in the pathogenesis of primary biliary cirrhosis (PBC). Recently, CD4-positive T helper type 17 (Th17) cells, characterized by the secretion of interleukin (IL)-17, have been implicated in the pathogenesis of autoimmune diseases. Human Th17 cells are generated from Th0 cells by IL-6 and IL-1β and maintained by IL-23. In this study, the role of IL-17 in PBC and its association with biliary innate immunity were examined. Using cultured human biliary epithelial cells (BECs), the expression of Th17-related cytokines and chemokines and changes therein on treatment with pathogen-associated molecular patterns (PAMPs) and IL-17 were examined. Immunohistochemistry for IL-17 and Th17-related cytokines was performed using tissue samples of human liver. Consequently, the expression of IL-6, IL-1β, IL-23p19 and IL-23/IL-12p40 mRNAs, and their up-regulation by PAMPs, were found in BECs. Moreover, BECs possessed IL-17-receptors and stimulation with IL-17 induced production of IL-6, IL-1β, IL-23p19 and chemokines. Several IL-17-positive cells had infiltrated damaged bile ducts and the expression of IL-6 and IL-1β was enhanced in the bile ducts of PBC patients. In conclusion, IL-17-positive cells are associated with the chronic inflammation of bile ducts in PBC which is associated causally with the biliary innate immune responses to PAMPs.

Original languageEnglish
Pages (from-to)261-270
Number of pages10
JournalClinical and Experimental Immunology
Volume157
Issue number2
DOIs
Publication statusPublished - Aug 1 2009

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Biliary Liver Cirrhosis
Interleukin-17
Innate Immunity
Interleukin-1
Interleukins
Interleukin-6
Bile Ducts
Interleukin-23
Th17 Cells
Epithelial Cells
Chemokines
Interleukin-17 Receptors
Cytokines
Autoimmune Diseases
Up-Regulation
Immunohistochemistry
Inflammation
Messenger RNA
Liver
Pathogen-Associated Molecular Pattern Molecules

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Periductal interleukin-17 production in association with biliary innate immunity contributes to the pathogenesis of cholangiopathy in primary biliary cirrhosis. / Harada, K.; Shimoda, Shinji; Sato, Y.; Isse, K.; Ikeda, H.; Nakanuma, Y.

In: Clinical and Experimental Immunology, Vol. 157, No. 2, 01.08.2009, p. 261-270.

Research output: Contribution to journalArticle

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