Interleukin-17-dependent autoimmunity to collagen type V in atherosclerosis.

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.

• Authors: 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
• Journal: Circulation research (Circ Res) Vol. 107 Issue 9 Pg. 1106-16 (Oct 29 2010) ISSN: 1524-4571 [Electronic] United States
• PMID: 20814021 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoproteins E
• Collagen Type V
• Interleukin-17

Topics

• 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)