title: Interleukin-17-dependent autoimmunity to collagen type V in atherosclerosis.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, 1300 University Ave., Madison, WI 53706, USA.
authors.forename: Melanie L
authors.initials: ML
authors.lastname: Dart
authors.forename: Ewa
authors.initials: E
authors.lastname: Jankowska-Gan
authors.forename: Guorui
authors.initials: G
authors.lastname: Huang
authors.forename: Drew A
authors.initials: DA
authors.lastname: Roenneburg
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Keller
authors.forename: Jose R
authors.initials: JR
authors.lastname: Torrealba
authors.forename: Aaron
authors.initials: A
authors.lastname: Rhoads
authors.forename: Byoungjae
authors.initials: B
authors.lastname: Kim
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Bobadilla
authors.forename: Lynn D
authors.initials: LD
authors.lastname: Haynes
authors.forename: David S
authors.initials: DS
authors.lastname: Wilkes
authors.forename: William J
authors.initials: WJ
authors.lastname: Burlingham
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Greenspan
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002417:Cattle; D024062:Collagen Type V / Q000009:adverse effects / Q000502:physiology*; D004195:Disease Models, Animal; D006801:Humans; D020381:Interleukin-17 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D001057:Apolipoproteins E; D024062:Collagen Type V; D020381:Interleukin-17
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