Inflammation and Regulation by Integrin Cell Adhesion Antagonists

Abstract The integrin family of cell adhesion molecules play a role in almost every phase of the immune response, from the induction of acute inflammation to its resolution, and antigen-specific immunity. Given these extensive roles, integrins have been actively targeted with both small molecule therapeutics and biologics to dampen pathological inflammatory responses and autoimmunity. Here we will discuss recent approvals of drugs targeting integrins in dry eye disease, inflammatory bowel disease, and other autoimmune diseases such as psoriasis and multiple sclerosis. We will also discuss novel approaches to target integrins by taking advantage of their conformational plasticity and the molecular mechanisms by which they transmit signals into cells. Even though the first therapeutics specific to integrins were approved over 2 decades ago, only 4 of the 24 known integrin heterodimers have been successfully targeted in the clinic. There remains much work to be done before our understanding of these cell adhesion receptors can be fully exploited for therapeutic benefit.