Novel Functions of Integrins as Receptors of CD154: Their Role in Inflammation and Apoptosis

Abstract

CD154, an inflammatory mediator also known as CD40 ligand, has been identified as a novel binding partner for some members of the integrin family. The αIIbβ3, specifically expressed on platelets, was the first integrin to be described as a receptor for CD154 after CD40. Its interaction with soluble CD154 (sCD154) highly contributes to thrombus formation and stability. Identifying αIIbβ3 opened the door for investigating other integrins as partners of CD154. The αMβ2 expressed on myeloid cells was shown capable of binding CD154 and contributing as such to cell activation, adhesion, and release of proinflammatory mediators. In parallel, α5β1 communicates with sCD154, inducing pro-inflammatory responses. Additional pathogenic effects involving apoptosis-preventing functions were exhibited by the CD154–α5β1 dyad in T cells, conferring a role for such interaction in the survival of malignant cells, as well as the persistence of autoreactive T cells. More recently, CD154 receptors integrated two new integrin members, αvβ3 and α4β1, with little known as to their biological significance in this context. This article provides an overview of the novel role of integrins as receptors of CD154 and as critical players in pro-inflammatory and apoptotic responses.