Induction of autoimmune cholangitis in non-obese diabetic (NOD).1101 mice following a chemical xenobiotic immunization

K. Wakabayashi, K. Yoshida, Patrick S Leung, Y. Moritoki, G. X. Yang, K. Tsuneyama, Z. X. Lian, T. Hibi, A. A. Ansari, L. S. Wicker, W. M. Ridgway, R. L. Coppel, I. R. Mackay, M. Eric Gershwin

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Our laboratory has suggested that loss of tolerance to pyruvate dehydrogenase (PDC-E2) leads to an anti-mitochondrial antibody response and autoimmune cholangitis, similar to human primary biliary cirrhosis (PBC). We have suggested that this loss of tolerance can be induced either via chemical xenobiotic immunization or exposure to select bacteria. Our work has also highlighted the importance of genetic susceptibility. Using the non-obese diabetic (NOD) congenic strain 1101 (hereafter referred to as NOD.1101 mice), which has chromosome 3 regions from B6 introgressed onto a NOD background, we exposed animals to 2-octynoic acid (2OA) coupled to bovine serum albumin (BSA). 2OA has been demonstrated previously by a quantitative structural activity relationship to react as well as or better than lipoic acid to anti-mitochondrial antibodies. We demonstrate herein that NOD.1101 mice immunized with 2OA-BSA, but not with BSA alone, develop high titre anti-mitochondrial antibodies and histological features, including portal infiltrates enriched in CD8 + cells and liver granulomas, similar to human PBC. We believe this model will allow the rigorous dissection of early immunogenetic cause of biliary damage.

Original languageEnglish (US)
Pages (from-to)577-586
Number of pages10
JournalClinical and Experimental Immunology
Volume155
Issue number3
DOIs
StatePublished - Mar 2009

Fingerprint

Inbred NOD Mouse
Cholangitis
Xenobiotics
Bovine Serum Albumin
Anti-Idiotypic Antibodies
Immunization
Biliary Liver Cirrhosis
Thioctic Acid
Immunogenetics
Chromosomes, Human, Pair 3
Genetic Predisposition to Disease
Granuloma
Pyruvic Acid
Antibody Formation
Dissection
Oxidoreductases
Bacteria
Liver
2-octynoic acid

Keywords

  • AMAs
  • Autoimmune cholangitis
  • NOD.1101 mice
  • PBC
  • Xenobiotic agents

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Induction of autoimmune cholangitis in non-obese diabetic (NOD).1101 mice following a chemical xenobiotic immunization. / Wakabayashi, K.; Yoshida, K.; Leung, Patrick S; Moritoki, Y.; Yang, G. X.; Tsuneyama, K.; Lian, Z. X.; Hibi, T.; Ansari, A. A.; Wicker, L. S.; Ridgway, W. M.; Coppel, R. L.; Mackay, I. R.; Gershwin, M. Eric.

In: Clinical and Experimental Immunology, Vol. 155, No. 3, 03.2009, p. 577-586.

Research output: Contribution to journalArticle

Wakabayashi, K, Yoshida, K, Leung, PS, Moritoki, Y, Yang, GX, Tsuneyama, K, Lian, ZX, Hibi, T, Ansari, AA, Wicker, LS, Ridgway, WM, Coppel, RL, Mackay, IR & Gershwin, ME 2009, 'Induction of autoimmune cholangitis in non-obese diabetic (NOD).1101 mice following a chemical xenobiotic immunization', Clinical and Experimental Immunology, vol. 155, no. 3, pp. 577-586. https://doi.org/10.1111/j.1365-2249.2008.03837.x
Wakabayashi, K. ; Yoshida, K. ; Leung, Patrick S ; Moritoki, Y. ; Yang, G. X. ; Tsuneyama, K. ; Lian, Z. X. ; Hibi, T. ; Ansari, A. A. ; Wicker, L. S. ; Ridgway, W. M. ; Coppel, R. L. ; Mackay, I. R. ; Gershwin, M. Eric. / Induction of autoimmune cholangitis in non-obese diabetic (NOD).1101 mice following a chemical xenobiotic immunization. In: Clinical and Experimental Immunology. 2009 ; Vol. 155, No. 3. pp. 577-586.
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