SKINIPEDIA - Skin Studies: Unlocking Skin's Secrets
Dr. Julie Segre: Unlocking Skin's Many Secrets
The National Human Genome Research Institute's (NHGRI) Dr. Julie Segre is fascinated by how the body responds to the world around it, so she focuses on the body's largest organ: the skin. "The skin is a major organ system that has to interact with and adapt to the environment," said Dr. Segre. "It's the interface between our complex physiology and an often hostile environment that dries us out and exposes us to chemicals and infectious agents. You don't want kitchen cleanser in your bloodstream and your skin is the way you keep it out."
Although Dr. Segre's research centers on just one organ, what she has discovered gives us more information on every tissue that has contact with the outside world, including the surface of the eye, the intestinal tract, and the mucus membranes in the nose and lungs. Her work may also help create treatments for conditions as diverse as psoriasis, asthma and dehydration in premature babies.
Psoriasis and eczema are the principal disorders that Dr. Segre studies. Both show up first on the skin, but can affect several other areas of the body. "These disorders are complex, multi-system problems," explained Dr. Segre, who is an investigator in the Genetics and Molecular Biology Branch of NHGRI's Division of Intramural Research. "If we can understand what happens with the skin, we may get clues about their underlying causes and how they create difficulties for us."
"While skin disorders primarily affect the quality of life, they can lead to serious problems if left untreated. Kids with eczema often develop asthma. Is it because the allergens that get in through breaks in the skin travel to the lungs or because one inflammatory process sets off another? We don't know yet, but we hope that if we learn how to manage eczema the patient won't develop asthma down the line. If they already have asthma, we hope that treating the skin problem will cause the asthma to improve."
Eczema starts between six months and one year of age with red, itchy patches that are sometimes mistaken for dry skin. The disorder is chronic, and the skin patches will come and go throughout life. Psoriasis usually develops between the ages of 20 and 30. Silvery patches form at places where the skin bends and breaks, such as knees and elbows. Psoriasis is also a chronic, relapsing condition and involves a lifetime of treatment. In the United States, 20 to 30 percent of the population has developed eczema, and 2 to 3 percent suffer from psoriasis.
Current medical wisdom says that both problems are caused by an overactive immune system that creates an allergic reaction in the skin, but Dr. Segre and her colleagues think that psoriasis and eczema can start with, rather than cause, skin breaks.
Role of the barrier in the skin's recovery from wounding
Once the skin barrier is broken, usually by a cut or scrape, allergens and infectious agents enter and start an inflammatory process. Most people heal the skin break quickly, and their immune system soon quiets down. However, the skin cells of people who have a genetic tendency towards psoriasis and eczema overreact to the challenge and get stuck in a cycle where the skin cells and the immune system stimulate each other in a continuous loop.
Schematic diagram of the stages of epidermal differentiation, resulting in a permeability barrier. Epidermal keratinocytes undergo a linear program of differentiation from mitotically active basal cells to transcriptionally active spinous cells to enucleated granular cells, resulting finally in differentiated squames in the stratum corneum. As shown in the inset, squames, which provide the primary barrier, are composed of keratin macrofibrils and cross-linked cornified envelopes encased in lipid bilayers. Tight junctions, located in the granular layer, also play an essential role in retaining the water content of the body. |
Role of barrier acquisition in the epidermal response to wound healing. Under normal conditions the epidermis serves as a barrier to retain water within the body and prevent the entry of infectious agents (e.g., microbes) or chemical agents. Dendritic Langerhans cells, resident in the epidermis, recognize, process, and present antigens to T lymphocytes. In response to trauma to the epidermis, depicted as a full-thickness epidermal wound, keratinocytes increase their proliferation rate and cytokine release. Keratinocytes proliferate and migrate to re-epithelialize the wounded area. T lymphocytes are recruited into the damaged skin. As part of the normal process, keratinocytes initiate the process of terminal differentiation to restore the epidermal barrier. However, if the process of terminal differentiation or barrier recovery is impaired, the skin can enter an inflammatory state. |
Although calming the immune system has been the major focus of most therapies for these disorders, Dr. Segre's laboratory made the practical discovery that healing the skin break is just as important as immune modulation for a good outcome. The group hopes that re-establishing the skin barrier, perhaps with a protective lotion or lipid bandage, will break the inflammatory loop and allow the immune system to stop reacting. That might mean that people with psoriasis and eczema would need lower doses of drugs and less treatment.
Dr. Julie Segre: Unlocking Skin's Many Secrets Part II is HERE.
