New discovery may ‘impact treatment of autoimmune diseases’

Scientists have found a way of “dictating” cell fate to ensure controlled production of helper and regulatory T cells.

A new study has found a way of manipulating the differentiation of T cells in the immune system so as to strike a balance between pro-inflammatory and anti-inflammatory cells. This discovery may have implications for treating autoimmune diseases and some types of cancer.

Autoimmune diseases are triggered when our immune system misidentifies healthy cells as foreign bodies and decides to attack them. In this process, certain cells called “T cells,” which are found in the immune system, are involved.

T cells are of different types and have distinct functions, but their main role is to mediate immune reactions in the body. Some T cells are pro-inflammatory, promoting an immune response, while others are immunosuppressive, regulating the “aggressiveness” of this response.

Autoimmune diseases, as well as some types of cancer such as colorectal cancer and lung cancer, are mediated by certain T cell imbalances in the immune system. These imbalances lead either to anomalous inflammations, or to a lack of reaction, wherein the body is unable to identify pathogens.

Recently, much research has been conducted into a particular type of T cells called “T helper 17” (Th17) cells. Studies have found that Th17 cells can be unstable, thus sustaining autoimmune diseases and mediating some cancers.

A new study led by Dr. Sheng Ding, from the Gladstone Institutes in San Francisco, CA, discovered a way of changing cell fate to determine differentiation either into Th17 cells, which are pro-inflammatory, or into regulatory T cells, which are immunosuppressive.

The researchers published their findings in the journal Nature.

“Our findings could have a significant impact on the treatment of autoimmune diseases, as well as on stem cell and immuno-oncology therapies,” says Dr. Ding.

Chemical compound key to cell manipulation
In this study, experiments were conducted both in vitro (using cell cultures) and in vivo (using mice) to test the effect of a chemical compound called “(aminooxy)acetic acid” (AOA).

The researchers found that AOA is key in “telling” a progenitor cell to specialize into either Th17 or regulatory T cells. This allows for the formation of strategies to help promote cellular balance within the immune system.

Dr. Ding and his colleagues explain that this discovery can have wider implications for cancer and autoimmune disease treatments.

Determining differentiation into regulatory T cells rather than Th17 in the case of autoimmune diseases, for instance, could inhibit the exacerbated inflammatory effect caused by the helper cells.

The researchers are also eager to investigate any potential benefits this strategy might bring to stem cell-driven therapy; regulatory T cells can sometimes be used to prevent the system from rejecting organ transplants.

Dr. Ding and his colleagues now suggest that production of regulatory T cells might also be used to promote immune tolerance of cell transplants. They have also expressed their hope that the same strategy might prove effective – albeit indirectly – in cancer therapy.

“Our work could also contribute to ongoing efforts in immuno-oncology and the treatment of cancer. This type of therapy doesn’t target the cancer directly, but rather works on activating the immune system so it can recognize cancer cells and attack them.” – First author Dr. Tao Xu, Gladstone Institutes

While there is still some way to go in understanding how AOA might best be utilized to make treatments more effective, the researchers suggest that this is the first step in regaining control of faulty immune system mechanisms.


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