| Interleukin-17-dependent autoimmunity to collagen type V in atherosclerosis. | |
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MedLine Citation:
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PMID: 20814021 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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RATIONALE: Considerable evidence shows atherosclerosis to be a chronic inflammatory disease in which immunity to self-antigens contributes to disease progression. We recently identified the collagen type V [col(V)] α1(V) chain as a key autoantigen driving the Th17-dependent cellular immunity underlying another chronic inflammatory disease, obliterative bronchiolitis. Because specific induction of α1(V) chains has previously been reported in human atheromas, we postulated involvement of col(V) autoimmunity in atherosclerosis. OBJECTIVE: To determine whether col(V) autoimmunity may be involved in the pathogenesis of atherosclerosis. METHODS AND RESULTS: Here, we demonstrate Th17-dependent anti-col(V) immunity to be characteristic of atherosclerosis in human coronary artery disease (CAD) patients and in apolipoprotein E-null (ApoE(-/-)) atherosclerotic mice. Responses were α1(V)-specific in CAD with variable Th1 pathway involvement. In early atherosclerosis in ApoE(-/-) mice, anti-col(V) immunity was tempered by an interleukin (IL)-10-dependent mechanism. In support of a causal role for col(V) autoimmunity in the pathogenesis of atherosclerosis, col(V) sensitization of ApoE(-/-) mice on a regular chow diet overcame IL-10-mediated inhibition of col(V) autoimmunity, leading to increased atherosclerotic burden in these mice and local accumulation of IL-17-producing cells, particularly in the col(V)-rich adventitia subjacent to the atheromas. CONCLUSIONS: These findings establish col(V) as an autoantigen in human CAD and show col(V) autoimmunity to be a consistent feature in atherosclerosis in humans and mice. Furthermore, data are consistent with a causative role for col(V) in the pathogenesis of atherosclerosis. |
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Authors:
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Melanie L Dart; Ewa Jankowska-Gan; Guorui Huang; Drew A Roenneburg; Melissa R Keller; Jose R Torrealba; Aaron Rhoads; Byoungjae Kim; Joseph L Bobadilla; Lynn D Haynes; David S Wilkes; William J Burlingham; Daniel S Greenspan |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-09-02 |
Journal Detail:
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Title: Circulation research Volume: 107 ISSN: 1524-4571 ISO Abbreviation: Circ. Res. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-29 Completed Date: 2010-11-22 Revised Date: 2011-10-31 |
Medline Journal Info:
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Nlm Unique ID: 0047103 Medline TA: Circ Res Country: United States |
Other Details:
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Languages: eng Pagination: 1106-16 Citation Subset: IM |
Affiliation:
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Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, 1300 University Ave., Madison, WI 53706, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apolipoproteins E / deficiency, genetics Atherosclerosis / genetics, immunology*, pathology Autoimmune Diseases / genetics, immunology*, pathology Cattle Collagen Type V / adverse effects, physiology* Disease Models, Animal Humans Interleukin-17 / physiology* Mice Mice, Inbred C57BL Mice, Knockout Mice, SCID Th1 Cells / immunology, metabolism, pathology |
| Grant Support | |
ID/Acronym/Agency:
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1P01AI084853-01/AI/NIAID NIH HHS; HL067177/HL/NHLBI NIH HHS; R01 AR047746-14A2/AR/NIAMS NIH HHS; R01 AR047746-15/AR/NIAMS NIH HHS; R01 AR047746-16/AR/NIAMS NIH HHS; R01AI066219/AI/NIAID NIH HHS; R01AR047746/AR/NIAMS NIH HHS; R56 AR047746-14A1/AR/NIAMS NIH HHS; R56AR047746/AR/NIAMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Apolipoproteins E; 0/Collagen Type V; 0/Interleukin-17 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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