Targeted control of a type of immune cells called regulatory T-cells (Treg cells) may help treat patients with autoimmune diseases, including inflammatory bowel disease, and protect against cancer in patients prone to develop that disease, a new study suggests.
The study, “An Essential Role For The IL-2 Receptor In Treg Cell Function,” was published in the journal Nature Immunology. It showed that manipulating a protein called IL-2R helps achieve the desired activation and control of the immune system.
T-cells are a type of immune cells responsible for killing infected or cancer cells (cytotoxic T-cells) and for several immune responses (helper T-cells). The activity of these cells is regulated by Treg cells. As such, when Treg cells do not work properly, T-cells stimulate a series of abnormal immune reactions against the person’s own body. Sustained inflammation can then trigger gastrointestinal cancer.
Researchers already had shown that IL-2R was a key contributor for the production and maintenance of Treg cells, but did not understand exactly how this molecule influenced the activity of these regulatory cells.
Using mice, the team investigated how IL-2R-mediated signaling in Treg cells influenced the development of cancer in the small intestine in animals that were more susceptible to develop the disease.
They observed that while IL-2R activation is necessary for Treg cells to suppress the activity of helper T-cells and inflammation, the activation of Treg cells also leads to a reduction in the activity of cytotoxic T-cells, which no longer could prevent against cancer.
So, while the activation of Treg cells mediated by IL-2R may limit inflammatory reactions by controlling the activity of the helper T-cells, on the other, it also increases the risk of developing cancer by reducing the activity of the cytotoxic T-cells.
“Our findings suggest that regulatory T cells have a dual role in inflammation-associated [gastrointestinal] cancers, limiting precancerous lesions in the early stages, but promoting cancerous growths in later stages of the disease,” Alexander Rudensky, the senior author of the study, said in a press release.
According to Rudensky, one possible way to release the cytotoxic T-cells from the grasp of Treg cells “would be to provide them [Treg cells] with interleukin 2 in a targeted manner.” If possible, this targeted activation of Tregs would prove useful to treat several autoimmune and inflammatory diseases, including inflammatory bowel disease, while protecting against gastrointestinal cancer in these patients.