Unlocking a New Target to Treat Gut Inflammation

Immunologists have uncovered a molecular switch in T cells that serves as a prime target for therapeutics against inflammatory bowel disease, or IBS. 

Over 10 percent of the population is affected by IBS, yet we still don’t have a clear picture of the biology underlying the condition. The root cause is likely not one, but a combination of factors, including chronic inflammation, leaky gut syndrome, changes in the intestinal microbiome, and hypersensitivity to certain foods. 

On the hunt to bridge knowledge gaps in the field, a team of researchers took a closer look at an immune molecule known as the transmembrane activator and calcium modulator and cyclophilin ligand interactor, or TACI. 

Scientists had previously observed that TACI is expressed on antibody-producing B cells. However, researchers believed that TACI might also be transiently expressed on T cells, influencing their activity during autoimmune disorders. 

In their study, researchers used a knockout mouse model (lacking the TACI gene) to investigate immune cell dynamics during elevated gut inflammation. They found that the loss of TACI elevated the risk of severe flare-ups in the gut lining. Animals lacking TACI also spiraled more rapidly after IBS onset: they lost weight and showed signs of extensive damage to the colon lining. Many more TACI-negative animals did not survive the extreme IBS symptoms compared to the control group. 

Ultimately, the researchers demonstrate that TACI is a potent orchestrator of gut inflammation, and stimulating TACI expression in IBS patients' immune cells may help relieve symptoms. 

According to the researchers, the implications of their findings go beyond IBS. “Besides extending the diverse roles TACI plays in various immune cell types to CD4+ T cells, our findings advance the understanding of the context-specific mechanisms governing TACI function that will inform the development of new therapeutics to target TACI for the amelioration of autoimmune diseases, infection, and cancer,” wrote the authors.