IT MIGHT be just a scratch, but for some children a minor cut could be the first step in the development of skin conditions such as eczema and psoriasis, and even asthma and hay fever.
These illnesses all involve chronic inflammation of the protective tissues that line the body鈥檚 surfaces: the skin and the linings of the lungs, eyes, nasal passages and throat. Treatments have traditionally focused on dampening down the overactive immune response to allergens, but there is more and more evidence that the immune system is only half the story.
This week, Julia Segre at the US National Human Genome Research Institute in Bethesda, Maryland, and her colleagues report that damage to the skin may cause overproduction of a skin protein called connexin 26 (Cx26) in individuals possessing a defective form of the gene Cx26. The gene is is usually switched on in response to damage to the skin, where it stimulates the proliferation of new skin cells and binds the remaining ones together. In healthy individuals, Cx26 is switched off once the cell-to-cell connections are restored, but in people with a mutated form of the gene, including those suffering from psoriasis, elevated levels of Cx26 persist.
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鈥淚f the skin is compromised early in life, allergens may interact with immune cells, leading to a hyper-vigilant immune system鈥�
Segre created mice that had been genetically altered to overproduce Cx26. She found that these mice spontaneously produced sores like those seen in people with psoriasis (The Journal of Clinical Investigation, DOI: 10.1172/JCI27186).
鈥淥verproduction of Cx26 leads to such rapid proliferation of skin cells that they don鈥檛 have time to differentiate properly,鈥� says Segre. 鈥淭hese poor-quality cells do not link up correctly with their neighbours to reseal the protective barrier, nor do they send correct chemical signals to switch off the Cx26 gene.鈥� Allergens are then able to pass through the compromised skin and trigger inflammation. This in turn stimulates further growth of skin cells, leading to the inflamed, scaly skin associated with psoriasis, she says.
A similar mechanism may be at work in allergic conditions such as asthma and hay fever. Normally, airborne allergens such as pollen would not come into contact with the cells that trigger an immune response, but if the skin鈥檚 protective barrier is compromised early in life, this may increase the opportunities for allergens to penetrate to where they can interact with immune cells, leading to a hyper-vigilant immune system. Subsequent exposure to the allergen could then trigger allergic symptoms such as hay fever or asthma.
Segre鈥檚 paper is further evidence for the importance of a well-functioning skin barrier in preventing allergic disorders later in life. Last month, David McLean and his colleagues at the University of Dundee, UK, reported that a common mutation in the gene for a barrier-forming skin protein called filaggrin is associated with an increased risk of eczema and asthma in children (Nature Genetics, vol 367, p 1412).
鈥淭his is despite filaggrin not being found in lung epithelial tissue,鈥� says McLean. 鈥淭hese people are susceptible to antigens and allergens invading their body through their skin. This means their immune system is primed towards allergens that the rest of the population hasn鈥檛 been exposed to.鈥� The result is a much higher susceptibility to eczema, food allergies, asthma and hay fever, he says.
