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Human immune system is working every day to prevents bacteria, viruses, and parasites, attacks. It can also detects cells damage. Research led by Lancaster University has discovered how skin cells alert the immune system, when their DNA is damaged in the absence of infection. This DNA damage can come from a variety of sources, such as the sun’s UV rays, chemical agents like cigarette smoke, or from genotoxic drugs used in chemotherapy.
Skin is the primary barrier against the outside world, and is constantly exposed to viruses, bacteria, UV light and environmental toxins. The study found that DNA damage can lead to an immune response similar to what is observed during viral infection. Scientists damaged the DNA in skin cells using the chemotherapy drug Etoposide, and found that the damage was detected by some of the proteins in the cell that also recognise DNA from viruses.
The damaged skin cells produced immune messenger molecules such as interferons and other cytokines that usually alert the body to infections. While this response required many components of anti-viral defences, it activated them in a different way, making use of the proteins that are responsible for repairing human DNA after damage. Using CRISPR-Cas9 gene editing technology, researchers were able to modify skin cells to delete certain immune genes and determine their role in this pathway.
The research focused on components of the DNA sensing pathway that human cells deploy to detect viruses. Our cells use the protein cGAS to recognise virus DNA in the cytoplasm. cGAS then activates the immune adaptor STING (STimulator of INterferon Genes), which switches on an anti-viral immune response. The scientists found that STING could be activated in a different way after DNA damage, even when cGAS was absent. This involved a DNA binding protein in the nucleus, IFI16, which could activate STING with help from DNA repair factors.
They discovered a new way in which cells can switch on an immune response in the skin. It is possible that immune cells use this alarm system to detect damaged skin cells and prevents them from becoming cancerous.