With a powerful army of cells and molecules, the immune system defends the body against potentially harmful viruses, bacteria and other microorganisms in our environment. For those with autoimmune conditions, however, the immune system turns against them, mistakenly targeting the body’s tissues.
Among the cellular triggers known to be involved in autoimmune diseases is the transmembrane activator and calcium modulator and cyclophilin ligand interactor, or TACI. While TACI has been extensively studied in immune cells including B cells, its role in T cell physiology has been largely unexplored—a field that experts say could hold clues about autoimmune conditions such as inflammatory bowel disease (IBD).
“We surmised that the lack of clear evidence for TACI expression in T cells may be indicative of precise and temporal regulation of its expression,” explained Andy Tan, lead author and Senior Scientist and Group Leader at A*STAR’s Bioprocessing Technology Institute (BTI).
Tan and Lam Kong-Peng, Executive Director of A*STAR’s Singapore Immunology Network (SIgN), led a first-of-its-kind study to investigate TACI expression in different subsets of T cells and its potential role in IBD.
Using a mouse-derived cell culture model, the researchers established that TACI expression was strongly induced in a subset of helper T cells producing interleukin 17A called TH17 cells. TACI expression was not detected in other subsets such as TH1 cells producing interferon gamma or TH2 cells producing interleukin 4.
The team further investigated these findings in mice that were genetically engineered to delete the TACI gene. These animals were found to be more susceptible to severe intestinal disease than control mice, due to the presence of significantly higher numbers of TH17 cells.
Based on these observations, Tan and colleagues went on to explore how TACI deficiency may contribute to IBD progression. After chemically inducing gut inflammation in the animals, the team found that TACI-deficient mice developed more aggressive disease symptoms, losing weight much more rapidly, and sustaining greater damage to their colonic lining, with many animals succumbing to the uncontrolled inflammation.
“The key takeaway is that our findings collectively ascribe a T cell-intrinsic role for TACI in constraining TH17 pathogenicity and gut inflammation,” said Tan, who added that these data could inform the development of new therapeutics targeting TACI for flipping the switch on TH17-mediated autoimmune diseases including IBD and psoriasis.
In the future, Tan and his team plan to take a closer look at TACI expression in healthy individuals versus IBD patients, and whether TACI expression influences the composition of the gut microbiome, another factor known to exacerbate IBD.
The A*STAR-affiliated researchers contributing to this research are from the Bioprocessing Technology Institute (BTI) and the Singapore Immunology Network (SIgN).
