Workshop speakers in the spotlight: Esther Lutgens and Ziad Mallat

Prof. Esther Lutgens, The Netherlands

Esther Lutgens is Professor of Vascular Immunopathology, Academic Medical Center, University of Amsterdam, The Netherlands. Her research group is focused on the role of the immune system in atherosclerosis. She has shown that the inhibition of specific inflammatory responses can counteract the complications of atherosclerosis. Her current research interests include the role of the CD40-CD40 ligand signalling system in atherosclerosis development and progression.

Prof. Ziad Mallat, UK

Ziad Mallat is currently British Heart Foundation Professor of Cardiovascular Medicine, University of Cambridge, UK. His research group is focused on regulation of the immuno-inflammatory response in atherosclerosis. Specifically, his group has shown that defective clearance of apoptotic cells impairs the regulatory immune response in atherosclerosis and accelerates lesion development. Current research activities include the role of the regulatory immune response in the prevention and/or treatment of plaque vulnerability.

Atherosclerosis is a chronic inflammatory disease which is driven by innate and adaptive immune responses. Inflammation controls the development and the destabilisation of arterial plaque. Regulatory T cells play a critical role by inhibiting vascular inflammation, thereby protecting against lesion development and inflammation. Cytokines play a dual role in this process mediating both proinflammatory and antiinflammatory effects. Thus, induction of a specific regulatory T cell response to atherosclerosis-relevant antigens would be an attractive strategy to limit the development and progression of atherosclerosis through the promotion of immune tolerance.

In addition, the CD40-CD40 ligand (CD40L) signalling axis plays a key role in immunological pathways implicated in atherosclerosis. In an experimental model, inhibition of the CD40-CD40L system promoted the development of a stable atherosclerotic plaque. Therefore, targeting specific components of the CD40-CD40L pathway may offer the potential for reduced atherosclerosis and improved plaque stability. In addition, recognition that self DNA (i.e. released from dying cells or neutrophil extracellular traps) may stimulate autoimmune activation and atherosclerosis lesion formation, may provide a basis for novel therapeutic targets in the future.

Understanding Innate and adaptive immunity in atherosclerosis remains a key focus of research directed at promoting protective immune responses in atherosclerosis.

Key references

Döring Y, Manthey H, Drechsler M, Lievens D, Megens R, Soehnlein O, Busch M, Manca M, Koenen RR, Pelisek J, Daemen MJ, Lutgens E, Zenke M, Binder CJ, Weber C, Zernecke A. Auto-antigenic protein-DNA complexes stimulate plasmacytoid dendritic cells to promote atherosclerosis. Circulation 2012 [Epub ahead of print]

Engel D, Beckers L, Wijnands E, Seijkens T, Lievens D, Drechsler M, Gerdes N, Soehnlein O, Daemen MJ, Stan RV, Biessen EA, Lutgens E. Caveolin-1 deficiency decreases atherosclerosis by hampering leukocyte influx into the arterial wall and generating a regulatory T-cell response. FASEB J 2011;25:3838-48.

Herbin O, Ait-Oufella H, Yu W, Fredrikson GN, Aubier B, Perez N, Barateau V, Nilsson J, Tedgui A, Mallat Z. Regulatory T-cell response to apolipoprotein b100-derived peptides reduces the development and progression of atherosclerosis in mice. Arterioscler Thromb Vasc Biol 2012;32:605-12.

Van Vré EA, Ait-Oufella H, Tedgui A, Mallat Z. Apoptotic cell death and efferocytosis in atherosclerosis. Arterioscler Thromb Vasc Biol 2012 [Epub ahead of print].

Forrás: The European Atherosclerosis Society website