Scientists have reported a possible new way to reduce the risk of graft-versus-host disease (GvHD) after allogenic bone marrow transplant.
The team, from the Medical University of South Carolina, USA, took a close look at a molecule called stimulator of interferon genes (STING).
STING has multiple, apparently conflicting roles in the immune system. STING signalling is important in healthy autoimmunity and protection from tumour development. However, it can also suppress these functions. In addition, STING signalling in the transplant recipient’s cells can either protect against or promote graft-versus-host disease.
"We think that STING must have different roles in different cells," said lead researcher Dr Yongxia Wu. So, in a mouse model of allogenic stem cell transplant, they looked at different cell subsets to try and understand which cells were most impacted by STING.
They removed STING from either the recipient or the donor mice to examine what determines the direction of the STING response. The team found that if STING is absent in the transplant recipient, the donor’s T cells are more likely to attack the recipient’s healthy tissue and a more severe GvHD develops.
“STING deficiency resulted in increased survival, activation, and function of cells including macrophages and dendritic cells, resulting in accelerated/exacerbated graft-versus-host disease,” the team wrote in the journal Cellular and Molecular Immunology.
Conversely, a drug which over-activates STING before transplant significantly reduced the severity of GvHD, raising the possibility of a treatment to prevent GvHD.
“In conclusion, we revealed a novel role of STING that dictates T-cell allogeneic responses and validated STING as a potential therapeutic target for controlling graft-versus-host disease after allogenic haematopoietic cell transplantation,” they write.
The team are now carrying out further research to understand the biological functions of STING, including why it has different roles in different immune cells.
Wu Y, Tang CA, Mealer C, Bastian D, Hanief Sofi M, Tian L, Schutt S, Choi HJ, Ticer T, Zhang M, Sui X, Huang L, Mellor AL, Hu CA, Yu XZ. (2021) “STING negatively regulates allogeneic T-cell responses by constraining antigen-presenting cell function.” Cellular and Molecular Immunology, doi: 10.1038/s41423-020-00611-6
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