People who have inadequate vitamin A in their diets are more susceptible to skin infection, yet how that vitamin affects skin immunity has been unclear. In a study published in Cell Host & Microbe, researchers shed some light on that mystery by identifying a previously unknown bacteria-killing protein on the epidermis that requires the vitamin to work.

The researchers found that one protein in the resistin-like molecule (RELM) family - RELMα - acts as an antibiotic to rapidly kill bacteria. Both RELMα, which is made by mice, and the corresponding human RELM family protein, called resistin, are stimulated by dietary vitamin A.

"RELMα is the first example of an antimicrobial protein that requires dietary vitamin A for its bacterial killing activity. This finding gives us an important clue about how the skin defends itself against infection, and how skin defense is regulated by the diet," said the corresponding author on the study.

Dermatologists use synthetic vitamin A, called retinoid, to treat acne, psoriasis, and other skin conditions, although how those drugs work has long been a mystery.

"If the skin immune system breaks down, infection ensues. Skin infections, from bacteria such as Streptococcus, are among the most common reasons people come to the emergency room," added a co-author.

The team's experiments in human tissue and mice illuminate a previously unappreciated link between diet and innate immunity of the skin, suggesting why vitamin A derivatives are effective treatments for skin disease, said the senior author.

In addition to identifying RELMα's unique feature - its requirement for dietary vitamin A to kill bacteria - the team showed that mice fed a diet deficient in vitamin A made no RELMα. The researchers also found that mice missing RELMα were more susceptible to infection and had different bacterial species on their skin compared with typical mice.

To study how the microbiome impacts immunity, the researchers used colony of germ-free mice - mice raised from birth without exposure to germs - and identified genes that are turned on when such mice are exposed to bacteria.

"When the skin encounters bacteria, cells respond by making molecules that help defend the skin against infection," the author explained.

"This study gives us a better understanding of how diet impacts the ability of the skin to defend itself against bacterial infection - but more research will be needed to determine how these findings will impact patients with inflammatory skin diseases such as acne and psoriasis," said the co-author.

https://www.utsouthwestern.edu/newsroom/articles/year-2019/bacteria-killing-protein.html

https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(19)30207-0