NEW RESEARCH has indicated that gene variants associated with leukaemia, can produce ‘rogue’ immune cells that drive autoimmune diseases. This could explain previous observations that patients with leukaemia were more likely to develop autoimmune diseases than the healthy patients. The new research, carried out by the Garvan Institute of Medical Research, Sydney, Australia, investigated this link and revealed that killer T cells appeared to be a key player in this association.
The researchers found that gene variations affecting a protein that controls killer T cell growth can turn them rogue. “We showed that these rogue killer T cells are driving the autoimmunity. They are probably one of the cell types most directly contributing to autoimmune disease,” explained Etienne Masle-Farquhar, Immunogenomics and Genomic Medicine Labs from the Garvan Institute of Medical Research.
The blood of children with rare inherited autoimmune diseases was investigated using novel high-resolution screening methods. Clustered regularly interspaced palindromic repeats/Cas9 was then used test the impact of altering protein signal transducers and activators of the transcription pathway 3 (STAT3). STAT3 is a critical protein in controlling the B and T cells of the immune system. The researchers found that altering this protein could cause rogue T cells to bypass immune check points and attach the body’s own cells.
“We can now go and look for T cells with STAT3 variations,” stated Chris Goodnow, Head of the Immunogenomics Lab from the Garvan Institute of Medical Research, explaining the tangible implications of this research. “Part of what is driving these rogue cells to expand as killer T cells is the stress-sensing pathways. There is a lot of correlation between stress, damage, and ageing. Now we have tangible evidence of how that is connected to autoimmunity.”
This research could be used in the future to develop screening technologies to identify cells at risk of turning rogue. For now, further study is needed to determine which autoimmune disease rogue T cells play a role in.
