The Therapeutic Potential of Targeting TL1A in a Spectrum of Inflammatory Disorders

Konstantina Kitsou,1 Georgios Kokkotis,2 Giorgos Bamias2 1National and Kapodistrian University of Athens, Athens, Greece; 2GI Unit, 3rd Department of Internal Medicine, Sotiria Hospital, National and Kapodistrian University of Athens, Athens, GreeceCorrespondence: Giorgos Bamias, GI Unit, 3rd Academic Department of Internal Medicine, National and Kapodistrian University of Athens, Sotiria Hospital, Athens, Greece, Email gbamias@gmail.comAbstract: Tumor Necrosis Factor (TNF)-like cytokine 1A (TL1A) is a member of the TNFSF superfamily, with the ability to associate to Death Domain Receptor 3 (DR3) but also to Decoy Receptor 3 (DcR3). Functional signaling affects several DR3-bearing cells and critically regulates diverse immunological processes such as adaptive lymphocytic responses, homeostatic mucosal pathways, as well as fibrotic mechanisms. The multifaceted pleiotropic nature of the TL1A/DR3 system appears to be critically involved in the pathogenesis of inflammatory and autoimmune diseases, particularly Inflammatory Bowel Disease (IBD) and allergic lung inflammation and may represent a novel therapeutic target for patients. In fact, several clinical programs with anti-TL1A monoclonal antibodies are currently underway and initial results from clinical trials in patients with IBD report positive effects on clinical and endoscopical outcomes with favorable safety profile. In this narrative review, we aim to link the immunological characteristics of the TL1A/DR3 cytokine: receptor system with the pathogenesis of IBD but also other immune-mediated conditions by critically revisiting mechanistic evidence from animal models and associations with human disease states. We also review available information on the use of anti-TL1A monoclonal antibodies and comment on future challenges that may be associated with the therapeutic potential of targeting the TL1A/DR3 pathway.Keywords: TL1A, TNFSF15, DR3, autoimmunity, inflammation