Regulation of vascular inflammation in immunity and metabolic disease
Previous and current research
The scientific focus of our group is at the crossroads of Immunology, Inflammation, Vascular Medicine and Metabolism; we try to merge Basic Science and Translational Medicine by engaging preclinical translational models. We aim at identifying the role of mechanisms pertinent to immunology and vascular inflammation, especially leukocyte recruitment and activation, in the regulation of metabolic pathologies, such as the
development of insulin resistance and type 2 diabetes mellitus, the vascular complications of diabetes mellitus, especially diabetic retinopathy, as well as in inflammatory and autoimmune disorders.
(A) Cellular and molecular mechanisms of immune cell recruitment and activation in inflammatory and metabolic disease.
Our group studies the molecular mechanisms governing leukocyte-endothelial interactions in the course of metabolic, inflammatory disorders and autoimmune conditions (e.g. experimental autoimmune encephalomyelitis/multiple sclerosis). (i) We identified the anti-adhesive and anti-inflammatory functions of the Staphylococcus aureus-derived factor, Extracellular Adherence Protein (Eap), which is important for bacteria to subvert the host immune response. (ii) We have characterized a component of endothelial junctions,
Junctional Adhesion Molecule-C (JAM-C). JAM-C is a critical player during leukocyte transendothelial migration. (iii) Our work recently identified an endogenous inhibitor of the leukocyte adhesion cascade, the endothelial-derived developmental endothelial locus-1 (Del-1) that antagonizes integrin-dependent leukocyte adhesion to the endothelium and IL-17-dependent inflammation. (iv) We characterized pathways for leukocyte recruitment in the course of diabetes mellitus based on interactions of leukocyte integrin Mac-1 with the Receptor for advanced glycation endproducts. (v) We have identified an important role for platelets in mediating leukocyte recruitment in the course of neuroinflammation.
(B) Immunometabolism: Cellular and molecular mechanisms of the crosstalk between inflammation and metabolism.
Emerging evidence points to a major role of inflammation and immune cells, such as macrophages and T cells in metabolic organs, such as the adipose tissue or the liver for the development of obesity-related metabolic disease, such as insulin resistance, type 2 diabetes and non-alcoholic fatty liver disease. In this context, we are studying several pathways linking components of innate immunity (such as the complement system, macrophage polarisation or receptors involved in leukocyte recruitment) or of adaptive immunity (such as the co-stimulatory systems, CD40-CD40L and CD28-B7) to the development of obesity-related insulin resistance and liver disease.
(C) Crosstalk between inflammation and neovascularisation in retina disease, including diabetic retinopathy and retinopathy of prematurity.
Our group studies the crosstalk between inflammation / innate immunity and neovascularisation especially in the context of retina angiogenesis e.g. during vasoproliferative retinopathies, such as diabetic retinopathy and retinopathy of prematurity. (i) In this context we have demonstrated the angiogenesis-modulatory actions of components of the innate immunity, such as neutrophil-derived alpha-defensins, or the complement system. (ii) In addition, we have uncovered a link between pathways that signal DNA damage and mediate DNA-repair and hypoxia-induced neovascularisation in the course of proliferative retinopathies. We currently expand on these findings by analysing further pathways that mediate the response to cellular stress in endothelial cells in the course of vasoproliferative retina disease.