The potential of targeting TREM-1 in IBD.

Abstract

Innate immune dysfunction is a hallmark of the pathogenesis of Inflammatory Bowel Disease, both in Crohn's disease and ulcerative colitis. Despite considerable efforts in research to better understand the pathophysiology of IBD and for the development of new therapeutic modalities for IBD patients, there is no therapy specifically targeting the dysregulations of the innate immune response available today in that field. TREM-1 is exclusively expressed by innate immune cells and is an immune amplifier. Its engagement following the primary activation of Pattern Recognition Receptors, including Toll-Like Receptors, triggers the development of a dysregulated and sustained innate immune response, promoting the perpetuation of the inflammatory response in the mucosa of IBD patients, microscopic mucosal tissue alterations, impaired autophagy, impaired epithelial barrier integrity and function, ulcerations, and mucosal damages. In patients, TREM-1 activation is associated with the active status of the disease as well as with severity. Blocking TREM-1 in experimental colitis attenuates the dysregulated innate immune response leading to improved clinical signs. Anti-TREM-1 approaches have the potential of controlling the pathogenic dysregulation of the immune response in IBD by targeting an upstream amplification loop of the activation of innate immunity.