Gene variants associated with leukaemia can produce ‘rogue’ immune cells that drive autoimmune diseases, according to a new study.
Scientists had previously noticed that leukaemia patients were also likely to develop an autoimmune disease, such as rheumatoid arthritis or aplastic anaemia. Research into this link revealed that immune cells called killer T cells – responsible for destroying harmful cells and pathogens – were a key player.
This new research provides insight into the role these killer T cells play in leukaemia and autoimmune disease. Gene variations affecting a protein that controls the growth of killer T cells can turn them rogue, the researchers found.
“We showed that these rogue killer T cells are driving the autoimmunity. They’re probably one of the cell types most directly contributing to autoimmune disease,” says the lead author.
The findings are published in the journal, Immunity.
Cancers can grow when tumor cells are not identified or destroyed by the immune system. Autoimmune diseases occur when the immune system attacks the body’s own cells, mistaking them for harmful or foreign cells.
“We knew that people with various autoimmune diseases acquire these rogue killer T cells over time, but also that inflammation can cause immune cells to proliferate and develop mutations. We set out to discover whether the rogue T cells were causing these autoimmune conditions, or simply associated with them,” says the senior author.
The researchers used new high-resolution screening methods to look at blood from children with rare inherited autoimmune diseases.
They then used a technique called CRISPR/Cas9, a genome editing tool, in mouse models, to find out what happens when the protein STAT3 is genetically altered.
STAT3 is found throughout the body and is critical for various cell functions, including controlling the immune system’s B cells and T cells.
The team found that if these proteins are altered, they can cause rogue killer T cells to grow unchecked, resulting in enlarged cells that bypass immune checkpoints to attack the body’s own cells.
In addition, even just 1-2% of a person’s T cells going rogue could cause autoimmune disease.
“It’s never been clear what the connection between leukaemia and autoimmune disease is – whether the altered STAT3 protein is driving disease, or whether leukaemic cells are dividing and acquiring this mutation just as a by-product. It’s a real chicken-and-egg question, which Dr Masle-Farquhar's work has been able to solve,” says the senior author.
“This gives some really good cracks in the coalface of where we might do better in terms of stopping these diseases, which are sometimes life threatening,” the author says.
Future applications could include better targeting of medication, like already TGA-approved JAK inhibitors, based on the presence of these mutations. “We can now go and look for T cells with STAT3 variations. That’s a big step forward in defining who’s the bad guy,” says the author.
The study also identified two specific receptor systems – ways for cells to talk to one another – that are linked to stress.
“Part of what’s 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’s connected to autoimmunity,” the author says.
The team’s research may help develop screening technologies that clinicians could use to sequence the complete genome of every cell in a blood sample, to identify which cells might turn rogue and cause disease.
Further study is needed to determine whether rogue killer T cells are involved in all autoimmune diseases, and what proportion of people with rheumatoid arthritis and other autoimmune conditions have rogue cells and STAT3 variations.
https://www.cell.com/immunity/fulltext/S1074-7613(22)00591-X
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fstat3-gain-of-function&filter=22
Autoimmune diseases in leukemia linked to rogue immune cells
- 858 views
- Added
Latest News
Metabolic rewiring promotes…
By newseditor
Posted 18 Apr
A drug to prevent flu-induc…
By newseditor
Posted 18 Apr
New origin of deep brain waves
By newseditor
Posted 17 Apr
Starving cells hijack prote…
By newseditor
Posted 17 Apr
Miniature battery-free epid…
By newseditor
Posted 17 Apr
Other Top Stories
Stopping drug cravings with fewer side effects
Read more
Automated flow synthesis of proteins in the lab
Read more
Mechanism of action of anesthesia on consciousness solved!
Read more
Abnormal sperm and egg DNA crossover during cell division may cause…
Read more
Understanding transcriptome and matrisome control of wound healing…
Read more
Protocols
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Modular dual-color BiAD sen…
By newseditor
Posted 31 Mar
Publications
How does the microbiota con…
By newseditor
Posted 18 Apr
The integrated stress respo…
By newseditor
Posted 18 Apr
The immunobiology of herpes…
By newseditor
Posted 17 Apr
Circulating microbiome DNA…
By newseditor
Posted 17 Apr
Spindle oscillations in com…
By newseditor
Posted 17 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar