TL1A: a novel alarmin in airway, intestinal, and autoimmune disorders

The term alarmin denotes a broad class of molecules rapidly released to alert the immune system through the engagement of specific receptors on immune cells. Three alarmin cytokines, thymic stromal lymphopoietin (TSLP), IL-33, IL-25), are released from epithelial and certain stromal cells. TNF-like cytokine 1A (TL1A) is a member of the TNF cytokine superfamily, first identified in human endothelial cells. TL1A is now considered a novel alarmin expressed by human and mouse bronchial and intestinal epithelial cells. TL1A exerts its biological activities by binding to a trimeric receptor DR3 (death receptor-3), expressed on a wide spectrum of immune and structural cells (e.g., lung fibroblasts, endothelial cells, and bronchial epithelial cells). TL1A has been implicated in experimental and human inflammatory bowel diseases (IBD), airway inflammation and remodeling in severe asthma. A monoclonal antibody anti-TL1A (tulisokibart) is effective in inducing clinical remission in ulcerative colitis patients. Increasing evidence suggests that TL1A is also involved in certain autoimmune disorders (e.g., rheumatoid arthritis, psoriasis). These emerging findings broaden the role of TL1A in various human inflammatory conditions. Several clinical trials are currently evaluating the safety and efficacy of monoclonal antibodies targeting TL1A in asthma or IBD patients.