Research finds that skin location and type determine risk for conditions like psoriasis and atopic dermatitis – ScienceDaily

Two new studies from the University of California, Davis, explore how differences in skin composition may lead to skin diseases, such as psoriasis and atopic dermatitis.

“Skin does not have a uniform texture throughout the body,” said Emmanuel Maverakis, M.D., professor of dermatology and molecular medical microbiology at UC Davis and lead author on both studies. “Different properties of the skin at different body sites may influence the susceptibility of the skin to certain diseases.”

Skin diseases affect about 84.5 million Americans. Aging, trauma, environmental and genetic factors can lead to a wide range of skin diseases.

Body location determines skin structure, function, and susceptibility to disease

The skin is the largest organ in the body. They average about 20 square feet in size – that’s the size of a 4×5 room! The outer layer (the epidermis) contains a lipid matrix made up of free fatty acids, cholesterol, and ceramides (a family of waxy lipid molecules).

This class must face the environmental challenges specific to each area of ​​the body. For example, the skin of the face must be thin and elastic to accommodate facial expressions. The leather covering the heel must be thick and hard to withstand the force and protect it from the things we step on.

Skin formation depends on multiple factors, including the structure of the cutaneous barrier and the types of cells and genes it expresses.

Until recently, little was known about the cellular and molecular processes behind these differences. In the first study, researchers demonstrated the mechanisms that lead to these structural changes in the skin.

The epidermis has a “brick and mortar” structure: Molecules such as ceramides, cholesterol, and fatty acids form the “slurry,” and cells called keratinocytes are the “bricks.”

The researchers used single-cell sequencing to characterize how keratinocytes differ in different body locations. They also used targeted molecular profiling to describe the molecules that make up the “slurry” between keratinocytes. They then examined how these differences in gene expression matched compositional differences in the structure of lipids and proteins across body sites. These experiments explained why skin looks different at different body sites.

Compositional differences in skin lipids and proteins across different body sites may also explain why different skin diseases exist at different sites of the body. While characterizing the specific lipid changes associated with different skin diseases, the researchers discovered that fat sticking to a piece of tape applied to the skin was sufficient to diagnose a patient with a specific skin disease.

“These discoveries will lead to non-diagnostic tests for common skin diseases,” said co-lead author Alexander Merleaf, co-lead author of the project.

“These differences are also relevant to the future design of skincare products,” said Stephanie Lu, MD, a resident of dermatology and co-lead author of the study. “They show how skin care products must be specifically formulated to suit the particular body site to which they will be applied.”

Psoriasis and the immune system

In the second study, the research team studied how skin cells interact with the immune system.

Previously, it was known that keratinocytes can secrete substances that increase and reduce inflammation. Using single-cell sequencing to analyze each keratinocyte separately, the researchers observed that these immune-modifying molecules are expressed in certain layers of the epidermis.

Keratinocytes in the lower layer of the epidermis secrete immune and inflammatory molecules. This is to attract immune cells to the skin and stop them in place to wait patiently to fight off any pathogenic microbe or parasite that might breach the skin’s physical barrier. In contrast, they found that keratinocytes in the outer layer of the epidermis secrete pro-inflammatory molecules, particularly IL-36.

IL-36 is the main mediator of a subtype of psoriasis, an inflammatory skin disease. The team found that the amount of IL-36 in the skin is regulated by another molecule called PCSK9 and that individuals with variations in the PCSK9 gene have a predisposition to psoriasis.

“Our discovery that different layers of the skin secrete different immune mediators is an example of how the skin is highly specialized to interact with the immune system. Some people develop skin diseases, such as psoriasis, when there is an imbalance in the molecules secreted by the different layers of the skin.” Antonio G-said. Shaw, a UC Davis research fellow, is the study’s co-lead author.

Both studies have been published in JCI Insight.

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