Researchers uncover molecular mechanism behind rare immune disorder linked to STAT3 gene
Scientists from Australia, the US, and Japan have explained how a STAT3 gene mutation causes a rare inherited immune disorder, even with one healthy gene copy.
Key Takeaways
AIResearchers from the Garvan Institute of Medical Research and Sydney Children's Hospital in Australia, the US National Institute of Allergy and Infectious Diseases, and Hiroshima University in Japan have identified a molecular mechanism explaining how a mutation in a single copy of a gene responsible for immune regulation can cause a rare inherited immune disorder, even when the other gene copy remains healthy.
The study, published in the journal Science Signaling, found that the mutated form of the STAT3 protein not only loses its normal function but also binds to the healthy protein, preventing it from reaching the cell nucleus and disrupting gene expression regulation.
This defect is linked to hyper-IgE syndrome (HIES), a rare inherited immune disorder that can lead to recurrent skin and lung infections. STAT3 is a key regulator of gene expression in the immune system and responds to cytokine signals that coordinate immune responses.
Analyses showed that the mutation reduces the protein's ability to activate target gene expression, resulting in a weakened immune response. The discovered mechanism demonstrates how a single mutated gene copy can cause a dominant immune disorder by interfering with the function of the healthy protein.