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.