Apolipoprotein A-I and modulation of T cell functions

Objective

The pathogenesis of atherosclerosis involves inflammation and immune reactions. T cell responses contribute to local inflammation and growth of the atherosclerotic plaque. As intensified inflammatory activation may lead to local proteolysis, plaque rupture, and formation of a thrombus, studies of conventional and regulatory T cell functions during hypercholesterolemia are of outmost importance.
Low levels of high-density lipoprotein (HDL) cholesterol are associated with inflammatory and immune disorders, including atherosclerosis. Although accumulating evidence suggests that HDL has anti-inflammatory properties, and functions as a part of the immune system, the mechanisms by which HDL inhibits atherosclerosis are not yet fully understood.
Here, I propose to study the potential role of apoA-I in regulating the function of conventional and regulatory T cells. To this end, I will use hypercholesterolemic LDL receptor (LDLr) -/- and apoA-I-/- double knock-out (DKO) mice that develop severe atherosclerosis and display autoimmune phenotype, and, as a control, (LDLr) -/- single knock-out (SKO) mice fed atherogenic diet to study: 1) the role of apoA-I in regulating T cell motility, 2) the influence of apoAI on adhesion of T cells to antigen-presenting cells, 3) the effect of apoA-I on T-cell signaling molecules that regulate T cell motility and adhesion, 4) the relation between apoA-I and apoA-I-affected T-cell signaling molecules in vivo. These complementary approaches will allow me to investigate the role of apoA-I on regulating T cells functions, and will be indispensable to assess an impact of apoA-I-affected T-cell signaling molecules on atherosclerosis and autoimmune diseases.
As conventional T cells critically modulate atherosclerosis by promoting inflammation, and regulatory T cells display atheroprotective properties, mechanistic insights into how apoA-I regulates T cell functions will advance our understanding of the immune processes involved in atherosclerosis.

Fields of science

• medical and health sciences › basic medicine › immunology › autoimmune diseases
• medical and health sciences › clinical medicine › cardiology › cardiovascular diseases › arteriosclerosis

Programme(s)

• FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Topic(s)

• FP7-PEOPLE-2012-IEF - Marie-Curie Action: "Intra-European fellowships for career development"

Call for proposal

FP7-PEOPLE-2012-IEF
See other projects for this call

Funding Scheme

MC-IEF - Intra-European Fellowships (IEF)

Coordinator

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE

Address

Trinity Lane The Old Schools
CB2 1TN Cambridge
United Kingdom

Activity type

Higher or Secondary Education Establishments

EU contribution

€ 231 283,20

Administrative Contact

Renata Schaeffer (Ms.)