L’efficacité du CD154 monomérique dans le traitement des complications thrombotiques
CD154 has emerged as an important player in the pathogenesis of several autoimmune diseases, as well as vascular dysfunctions. CD154 is a member of the tumour necrosis factor family of pivotal importance in humoral immunity. However, CD154 also shares critical inflammatory functions through its interaction with its classical CD40 receptor or recently identified binding partners, namely αIIbβ3, α5β1 and αMβ2. These responses imply CD154 as a key factor in chronic inflammatory disorders including autoimmune diseases and thrombosis. Disrupting the interaction of CD154 with its receptors through anti-CD154 Abs significantly inhibits the development of these diseases, albeit serious side effects have been associated with these therapies. To overcome these adverse effects, other approaches such as knockout, antisense oligonucleotide and siRNA targeting were developed. These approaches were focused on the CD154/CD40 interaction and did not address the interaction of CD154 with its other receptors. Thus, there is a need for novel CD154 treatments for the prevention/abrogation of inflammatory or autoimmune diseases that address all CD154 receptors. Our group profoundly investigated the structural/functional interaction of CD154 with its various receptors. Given the importance of the trimeric structure of CD154 for its biological activity, we generated monomeric form of the molecule that can specifically bind to one receptor without inducing intracellular activation. This agent represents a potential therapeutic tool for the treatment of CD154-mediated diseases such as thrombotic events.
CD154 Mutant Receptor Monomer Thrombosis