The newly identified killer protein of bacteria needs vitamin A to work

People who have an inadequate diet of vitamin A are more susceptible to skin infections, but it is still unclear how this vitamin affects the immunity of the skin. In a study published today, researchers at UT Southwestern have cleared up this mystery by identifying on the epidermis a previously unknown protein that kills bacteria and needs this vitamin to act.

The researchers discovered that a family-resistant protein molecule (RELM) – RELMα – acts as an antibiotic to kill bacteria quickly. RELMα, made by mice, and the corresponding protein of the human RELM family, called resistin, are stimulated by dietary vitamin A.

"RELMα is the first example of an antimicrobial protein that requires vitamin A for its activity of eliminating bacteria.This discovery gives us an important clue to how the skin defends itself against infections and on regulating the immune system of the skin, "said Dr. Lora Hooper, chair of immunology and corresponding author of the study published in Cell Host & Microbe.

Dermatologists use synthetic vitamin A, called a retinoid, to treat acne, psoriasis and other skin conditions, although the functioning of these drugs has long been a mystery.

"The skin is the largest organ of the human body and is responsible for defending against infections," said Dr. Tamia Harris-Tryon, Assistant Professor of Dermatology and Immunology.

"If the immune system of the skin deteriorates, it results in an infection. Skin infections caused by bacteria such as streptococcus are among the most common causes of emergency room attendance," added Dr. Harris-Tryon, medical scientist having completed his postdoctoral training. in the Hooper laboratory.

Dr. Hooper is well known for her research on "commensal" or "good" bacteria in the intestine – it facilitates digestion and infection control.

The team's experiments on human tissues and mice highlight a previously unclear link between diet and innate immunity of the skin, suggesting why vitamin A derivatives are Effective treatments against skin diseases, said Dr. Hooper, a researcher at the Howard Hughes Medical Institute and also UTSW. Professor of Immunology and Microbiology with an additional appointment at the Center for Genetics of Host Defense. Dr. Hooper holds the Jonathan W. Uhr Distinguished Chair in Immunology and is a Nancy Cain and Jeffrey A. Marcus Fellow in Medical Research in the honor of Dr. Bill S. Vowell.

In addition to identifying the unique feature of RELMα – its need for dietary vitamin A to kill bacteria – the team showed that mice fed a vitamin A deficient diet did not manufacture RELMα. The researchers also found that mice lacking RELMα were more susceptible to infection and had different bacterial species on the skin compared to typical mice.

Dr. Harris-Tryon added, "Given the frequency of use of retinoids in dermatology, the results of our research are potentially vast, and skin is an important interface between us and the environment, and we need Defend Against Infections and Inflammation We are just beginning to understand how bacteria and the microbiome (the term that refers to the population of bacteria living with us) have an impact on skin diseases such as psoriasis and psoriasis. Our work helps define the molecules that the skin uses to create a healthy relationship between the microbiome and us, the hosts. "

To investigate the impact of the microbiome on immunity, the researchers used Hooper's mouse-free mouse colony (mice raised from birth without exposure to germs) and identified the genes activated when such mice are exposed to bacteria.

"When the skin meets bacteria, the cells react by making molecules that protect against infections," she said, adding that scientists from the National Institutes of Health (NIH) had collaborated in the study. study.

The researchers included some caveats.

"This study gives us a better understanding of the impact of diet on the skin's ability to defend itself against bacterial infections – but further research will be needed to determine how these results will affect disease patients." inflammatory skin conditions such as acne and psoriasis, "said Dr. Harris-Tryon, who earned her Ph.D. at Johns Hopkins University.