title: Co-stimulatory molecules in and beyond co-stimulation - tipping the balance in atherosclerosis?
abstract: A plethora of basic laboratory and clinical studies has uncovered the chronic inflammatory nature of atherosclerosis. The adaptive immune system with its front-runner, the T cell, drives the atherogenic process at all stages. T cell function is dependent on and controlled by a variety of either co-stimulatory or co-inhibitory signals. In addition, many of these proteins enfold T cell-independent pro-atherogenic functions on a variety of cell types. Accordingly they represent potential targets for immune-modulatory and/or anti-inflammatory therapy of atherosclerosis. This review focuses on the diverse role of co-stimulatory molecules of the B7 and tumour necrosis factor (TNF)-superfamily and their downstream signalling effectors in atherosclerosis. In particular, the contribution of CD28/CD80/CD86/CTLA4, ICOS/ICOSL, PD-1/PDL-1/2, TRAF, CD40/CD154, OX40/OX40L, CD137/CD137L, CD70/CD27, GITR/GITRL, and LIGHT to arterial disease is reviewed. Finally, the potential for a therapeutic exploitation of these molecules in the treatment of atherosclerosis is discussed.
authors: Institute for Cardiovascular Prevention, Ludwig-Maximilians University Munich, Munich, Germany. norbert.gerdes@med.uni-muenchen.de
authors: N
authors: N
authors: Gerdes
authors: A
authors: A
authors: Zirlik
mesh_terms: D000818:Animals; D001158:Arteries / Q000276:immunology*; D050197:Atherosclerosis / Q000276:immunology* / Q000628:therapy; D060887:B7 Antigens / Q000378:metabolism; D061025:Costimulatory and Inhibitory T-Cell Receptors / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007249:Inflammation / Q000276:immunology* / Q000628:therapy; D018836:Inflammation Mediators / Q000378:metabolism*; D008213:Lymphocyte Activation; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D060887:B7 Antigens; D061025:Costimulatory and Inhibitory T-Cell Receptors; D018836:Inflammation Mediators; D018124:Receptors, Tumor Necrosis Factor