A research team led by the University of Florida has discovered a mechanism that may help protect against skin diseases including psoriasis, eczema and even cataracts—all the same diseases accelerated by DNA damage.
Dangerous diseases, like psoriasis, eczema and cataracts (also called skin cancer) are increasingly appearing on the skin, with skin cancer constituting 60 percent of all cases. These diseases can be caused by the SIK2 gene mutation, which code for proteins that break down into tiny fragments that damage chromosomes. Scientists have previously identified a possible therapeutic role for one of those shreds called FLN10A, but like most proteins on the human genome, FLN10A only works properly when added to the gene to activate it.
“The flip comes when FLN10A is bound to DNA repair sites or in an immunodeficiency-inducing protein, like human leukocyte antigen, ” said the study’s lead author, Bunge Takahashi, Ph. D., chair of the U. of F’s Genitourinary, Immunologic and Cancer Biology Department and professor of Integrative Biology, Medicine, and Developmental Biology at the University of Florida. “In certain studies, FLN10A has been found replicated more often within mutated alleles of the SIK2 gene than in alleles that did not have SIK2-mutant genes—but this is the first time that FLN10A has been found in combination with other genes associated with skin diseases. “
The team’s findings are published in the journal Cell Reports.
Using a mouse model for psoriasis, which is caused by the skin damage caused by the loss of pigment from melanocytes, the team discovered that FLN10A helps protect against disease progression by blocking the damage healing process—helping to boost protective immunity, thus mitigating the damage the cell can do. This is a promising discovery because it was previously assumed that FLN10A could only work as a passive defense mechanism arising from preexisting immunity against other diseases, like skin cancer. But Takahashi’s study show FLN10A actually works to promote cancer cell recruitment into the affected areas making it a therapeutic target.
This study does not provide evidence that FLN10A activates other genes in skin genes and, therefore, is a factor in skin cancer. In addition, other studies have shown that synthetic versions of FLN10A that excite genes that are deficient in FLN10A may actually provoke cancer cells even though FLN10A is present in them and they have expressed FLN10A on their skin.
More studies are needed to confirm whether FLN10A boosts the effectiveness of immune checkpoint inhibitors—drugs that change the activities of the immune system—and their effectiveness against psoriasis.
“Many drugs we have looked at in this study have tried to remove FLN10A from immune cells to activate FLN10A, but treatment efforts to improve FLN10A function have not been successful because it does not happen as a side effect on CD4 T cells—a type of white blood cell that is a key driver of immune responses in the skin, ” Takahashi said. “I would like to see research scientists find other ways to activate FLN10A in skin cells, especially when activated in immune cells of the skin, including in vessels known as endothelium. “