| The role of natural killer (NK) and NK T cells in the loss of tolerance in murine primary biliary cirrhosis. | |
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MedLine Citation:
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PMID: 22519590 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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One of the major obstacles in dissecting the mechanism of pathology in human primary biliary cirrhosis (PBC) has been the absence of animal models. Our laboratory has focused on a model in which mice, following immunization with a xenobiotic chemical mimic of the immunodominant autoepitope of the E2 component of pyruvate dehydrogenase complex (PDC-E2), develop autoimmune cholangitis. In particular, following immunization with 2-octynoic acid (a synthetic chemical mimic of lipoic acid-lysine located within the inner domain of PDC-E2) coupled to bovine serum albumin (BSA), several strains of mice develop typical anti-mitochondrial autoantibodies and portal inflammation. The role of innate immune effector cells, such as natural killer (NK) cells and that NK T cells, was studied in this model based on the hypothesis that early events during immunization play an important role in the breakdown of tolerance. We report herein that, following in-vivo depletion of NK and NK T cells, there is a marked suppression of anti-mitochondrial autoantibodies and cytokine production from autoreactive T cells. However, there was no change in the clinical pathology of portal inflammation compared to controls. These data support the hypothesis that there are probably multiple steps in the natural history of PBC, including a role of NK and NK T cells in initiating the breakdown of tolerance. However, the data suggest that adaptive autoimmune effector mechanisms are required for the progression of clinical disease. |
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Authors:
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S Shimoda; K Tsuneyama; K Kikuchi; K Harada; Y Nakanuma; M Nakamura; H Ishibashi; S Hisamoto; H Niiro; P S C Leung; A A Ansari; M E Gershwin; K Akashi |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Clinical and experimental immunology Volume: 168 ISSN: 1365-2249 ISO Abbreviation: Clin. Exp. Immunol. Publication Date: 2012 Jun |
Date Detail:
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Created Date: 2012-04-23 Completed Date: 2012-06-20 Revised Date: 2013-06-05 |
Medline Journal Info:
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Nlm Unique ID: 0057202 Medline TA: Clin Exp Immunol Country: England |
Other Details:
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Languages: eng Pagination: 279-84 Citation Subset: IM |
Copyright Information:
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© 2012 The Authors. Clinical and Experimental Immunology © 2012 British Society for Immunology. |
Affiliation:
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Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Autoantibodies / blood Autoantigens / immunology Biomimetic Materials / chemistry Cattle Cells, Cultured Cytokines / blood Dihydrolipoyllysine-Residue Acetyltransferase / chemistry, immunology*, metabolism Disease Models, Animal Humans Immune Tolerance* Immunization Immunodominant Epitopes / chemistry Killer Cells, Natural / immunology, metabolism*, pathology Liver Cirrhosis, Biliary / immunology* Lymphocyte Depletion Mice Mice, Inbred C57BL Mitochondria / immunology*, metabolism Mitochondrial Proteins / chemistry, immunology*, metabolism Natural Killer T-Cells / immunology, metabolism*, pathology Peptide Fragments / administration & dosage, chemistry, metabolism Serum Albumin, Bovine / administration & dosage, chemistry Thioctic Acid / administration & dosage, chemistry, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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DK067003/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Autoantibodies; 0/Autoantigens; 0/Cytokines; 0/Immunodominant Epitopes; 0/Mitochondrial Proteins; 0/Peptide Fragments; 0/Serum Albumin, Bovine; 62-46-4/Thioctic Acid; EC 2.3.1.12/Dihydrolipoyllysine-Residue Acetyltransferase; EC 2.3.1.12/Dlat protein, mouse |
| Comments/Corrections | |
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