 |
 |
Menno van Lookeren Campagne Senior Scientist: Immunology |
The research projects in the van Lookeren Campagne lab are aimed at discovering novel receptors involved in innate immune response. Our current focus is on transmembrane receptors expressed on macrophages, immune cells whose primary function is to clear foreign pathogens, apoptotic cells and enteric microflora from the circulation. The lab recently discovered a Complement Receptor of the Ig-superfamily (CRIg) on macrophages that binds to activated complement component 3. Upon proteolytic activation, complement C3 covalently associates with pathogens and cell debris, and "paints" these particles for recognition by macrophages receptors including CRIg and complement receptors 1, 2, 3 and 4 (CR1-4). CRIg is required for an optimal innate immune defense by rapidly recognizing and phagocytosing pathogens in the circulation, preventing systemic bacteremia. In addition to its function as a phagocytic receptor, the extracellular domain of CRIg has potent complement inhibitory activity and can inhibit establish disease in experimental arthritis. Though CRIg shares ligands with CR1-4, it displays some unique features. In contrast to CR1-4, CRIg constitutively recycles on endosomes and functions as a phagocytic receptor in the absence of activation signals.
Apart from these basic research efforts, the lab collaborates with the Protein Engineering and Protein Chemistry Departments to better understand the structural basis of complement activation and inhibition. These efforts resulted in the first crystal structure of the central complement component C3b in complex with one of its receptors, CRIg. Additional structures of ligand-receptor complexes are being solved with the ultimate goal to apply structure-based design to generate more potent inhibitors of the complement cascade for treatment of complement-mediated diseases in the clinic.