Chemokines as therapy for autoimmunity
When our immune system malfunctions, it starts targeting ‘self’ antigens as foreign, giving rise to autoimmune or chronic inflammation disorders. Existing treatment strategies entail the use of immunosuppressive medications in order to slow down or suppress immune responses in an attempt to stop the inflammation involved in the disease. However, these drugs also suppress the ability of the immune system to fight infection, inducing other potentially serious side-effects. Therefore, the goal of the EU-funded ‘Innovative chemokine-based therapeutic strategies for autoimmunity and chronic inflammation’ (Innochem) project was to find alternative therapies and in particular to test the chemokine system as a new therapeutic target. Chemokines are cytokines capable of inducing chemotaxis, the ability of cells to move towards the site of infection or any compound gradient. They could also have a homeostatic role controlling the migration of cells, for example, during development. The Innochem approach aimed to specifically target part of the chemokine system that causes the adverse inflammatory responses. By using proteomics and various genetic pre-clinical models of autoimmune disorders, the INNOCHEM consortium obtained important data implicating chemokines and their receptors in various autoimmune/chronic inflammation disorders. Molecular analyses aided the dissection of the mechanisms underlying these diseases and led to the identification of key molecules. A series of antagonistic compounds were generated, including decoy receptors, agonist binders, and non-competitive allosteric inhibitors targeting the chemokines or their receptors. The interactions between agonists and antagonists, or inhibitors with the chemokine receptors were modelled, generating invaluable information for future drug design. Innochem’s complementary non-overlapping approach to target the chemokine system with recombinant and low molecular weight molecules is envisaged to provide an improved therapeutic strategy against autoimmunity and chronic inflammatory disorders.