Interleukin-17-dependent autoimmunity to collagen type v in atherosclerosis

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

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1106-1116
Number of pages11
JournalCirculation Research
Volume107
Issue number9
DOIs
StatePublished - Oct 29 2010

Fingerprint

Collagen Type V
Interleukin-17
Autoimmunity
Atherosclerosis
Collagen
Autoantigens
Apolipoproteins E
Coronary Artery Disease
Immunity
Atherosclerotic Plaques
Interleukin-10
Chronic Disease
Adventitia
Bronchiolitis
Collagen Type I
Cellular Immunity
Disease Progression

Keywords

  • atherosclerosis
  • autoimmunity
  • collagen type V
  • interleukin-17

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Dart, M. L., Jankowska-Gan, E., Huang, G., Roenneburg, D. A., Keller, M. R., Torrealba, J. R., ... Greenspan, D. S. (2010). Interleukin-17-dependent autoimmunity to collagen type v in atherosclerosis. Circulation Research, 107(9), 1106-1116. https://doi.org/10.1161/CIRCRESAHA.110.221069

Interleukin-17-dependent autoimmunity to collagen type v in atherosclerosis. / Dart, Melanie L.; Jankowska-Gan, Ewa; Huang, Guorui; Roenneburg, Drew A.; Keller, Melissa R.; Torrealba, Jose R.; Rhoads, Aaron; Kim, Byoungjae; Bobadilla, Joseph L.; Haynes, Lynn D.; Wilkes, David S.; Burlingham, William J.; Greenspan, Daniel S.

In: Circulation Research, Vol. 107, No. 9, 29.10.2010, p. 1106-1116.

Research output: Contribution to journalArticle

Dart, ML, Jankowska-Gan, E, Huang, G, Roenneburg, DA, Keller, MR, Torrealba, JR, Rhoads, A, Kim, B, Bobadilla, JL, Haynes, LD, Wilkes, DS, Burlingham, WJ & Greenspan, DS 2010, 'Interleukin-17-dependent autoimmunity to collagen type v in atherosclerosis', Circulation Research, vol. 107, no. 9, pp. 1106-1116. https://doi.org/10.1161/CIRCRESAHA.110.221069
Dart ML, Jankowska-Gan E, Huang G, Roenneburg DA, Keller MR, Torrealba JR et al. Interleukin-17-dependent autoimmunity to collagen type v in atherosclerosis. Circulation Research. 2010 Oct 29;107(9):1106-1116. https://doi.org/10.1161/CIRCRESAHA.110.221069
Dart, Melanie L. ; Jankowska-Gan, Ewa ; Huang, Guorui ; Roenneburg, Drew A. ; Keller, Melissa R. ; Torrealba, Jose R. ; Rhoads, Aaron ; Kim, Byoungjae ; Bobadilla, Joseph L. ; Haynes, Lynn D. ; Wilkes, David S. ; Burlingham, William J. ; Greenspan, Daniel S. / Interleukin-17-dependent autoimmunity to collagen type v in atherosclerosis. In: Circulation Research. 2010 ; Vol. 107, No. 9. pp. 1106-1116.
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