According to recent research from the Garvan Institute of Medical Research, “rogue” immune cells that cause autoimmune illnesses can be produced by gene variations linked to leukemia.
There was a correlation between leukemia and autoimmune diseases including rheumatoid arthritis and aplastic anemia, which had been noted by scientists before. Killer T cells, an immune cell type responsible for eliminating dangerous cells and infections, were shown to play a significant role in studies investigating this connection.
The function of killer T cells in leukemia and autoimmune diseases is explained by these novel findings. According to the study’s findings, killer T cells can be become aggressive due to mutations in genes responsible for producing a protein that regulates their expansion.
The researchers demonstrated that the autoimmune response is being driven by rogue killer T cells. Indeed, they may be one of the cells most responsible for autoimmune disorders according to a researcher at the Immunogenomics and Genomic Medicine Labs at Garvan University, Dr. Etienne Masle-Farquhar.
To aid in future treatment, the research also narrows down a few pathways that could be beneficial in targeting these cells.
The study’s results were just published in Immunity.
When the immune system fails to recognize and eliminate tumor cells, cancer can progress. As the name implies, autoimmune disorders manifest when the immune system mistakenly attacks healthy bodily tissue.
The researchers already knew that persons with autoimmune illnesses tend to create rogue killer T cells over time, and that inflammation might lead to immune cell proliferation and abnormalities. They aimed to learn if rogue T cells were primary or correlative of these autoimmune disorders according to Masle-Farquhar.
Researchers examined blood samples from children with uncommon hereditary autoimmune illnesses using cutting-edge high-resolution screening techniques.
Next, they employed CRISPR/Cas9, a genome editing technology, to study the effects of STAT3 gene editing in animal models.
STAT3 is ubiquitous and essential for many cell activities, including regulation of immune system B cells and T cells.
Researchers discovered that tampering with these proteins leads to the uncontrolled expansion of killer T cells, which then assault the body’s own cells because they are too large to be stopped by the immune system.
Furthermore, autoimmune illness can be caused by as little as 1%-2% of T cells in the body turning wild.
There has been much debate about whether the mutated STAT3 protein is the true cause of autoimmune illness, or whether leukaemic cells simply acquire this mutation during cell division.
The researchers add this finding gives some very excellent cracks in the coalface of where they may do better in preventing these potentially fatal infections.
Possible future uses include using the existence of these mutations to more precisely target medicine, such as JAK inhibitors that have previously been authorized by the TGA. Res that the researchers know where to search, they can begin identifying T cells with STAT3 mutations. That’s quite helpful in pinpointing the villain, they added.
The research also uncovered two distinct receptor systems, or cellular communication pathways, that are associated with stress.
The stress-sensing pathways may play a role in the proliferation of these rogue cells into killer T cells. Stress, injury, and the ensuing effects of old age all have strong ties to one another. Now that the link to autoimmunity has been established.
The findings of the researchers have the potential to aid in the development of screening technologies that physicians may use to sequence the whole genome of every cell in a blood sample, in order to determine which cells are more likely to become cancerous or otherwise malignant.
It is unclear if rogue killer T cells play a role in all autoimmune disorders or what percentage of persons with rheumatoid arthritis or other autoimmune ailments have rogue cells and STAT3 mutations, but this is an area that needs more research.
Sources:
Christopher C. Goodnow, STAT3 gain-of-function mutations connect leukemia with autoimmune disease by pathological dysregulation and accumulation of NKG2Dhi CD8+ T cells, Immunity (2022). DOI: 10.1016/j.immuni.2022.11.001
https://medicalxpress.com/news/2022-11-rogue-immune-cells-linked-leukemia.html
