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A team has shown that the activation of STING is a new molecular target in the fight against graft versus host disease (GVHD).
A new target molecule has been identified in the fight against graft versus host disease (GVHD). Bone marrow transplants, a treatment for some blood cancers, are accompanied by life-threatening GVHD in nearly 50% of patients. The study was conducted at the University of South Carolina Medicine (MUSC), United States.
Activating a molecule called an interferon gene stimulator (STING) may be a new approach to reducing the effects of GVHD, the researchers say. The team points out that data from other groups has shown that STING activation in T cells helps immune cells fight cancer.
In contrast, in the case of GVHD, T cells attack the body. Based on previous data, the researchers hypothesized that high activation of STING would be negative against the background of GVHD and lead to fighting the body’s immune system.
The team used a mouse model to test this hypothesis. The model was induced by a bone marrow transplant, which closely models the development of the disease in humans.
The researchers used the models to determine whether GVHD improved or worsened when STING was:
- absent in donor immune cells
- absent in the recipient’s immune cells
- overexpressed in the immune cells of the recipient.
They showed that the severity of GVHD was not altered when STING was absent from donor immune cells. However, GVHD was more severe and mortality rates were higher when STING was absent from the recipient’s immune cells.
The team then looked at different subsets of cells to try to understand which cells were most affected by the loss of STING. They found that the expression of STING in the antigen presenting cells of the recipient mouse (dendritic cells) reduced the expansion of donor T cells and the ability to migrate after a bone marrow transplant. This made it less likely that the T cells in the recipient mouse would attack its cells and lead to GVHD.
This finding was confirmed using a pharmacological drug that activated the STING molecule. The researchers say this suggests the possibility that a drug that activates STING may protect bone marrow transplant recipients from GVHD.
The article was published in Cellular and molecular immunology.
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