From eczema to asthma (in mice)

ResearchBlogging.orgEczema and asthma often co-occur, indeed, I suffer from both (albeit mildly). What I wasn’t aware of was that eczema often comes first. Though eczema often precedes asthma (asthma has an underlying rate of 4-8% in the general population, but 70% in individuals with a history of chronic severe eczema), the underlying mechanism for this so called ‘atopic march’ isn’t known, though work published today in PLoS Biology elucidates a possible mechanism.

Researchers genetically engineered mice with chronic skin barrier defects (mice lacking Notch signalling in the skin, leading to impairment of epidermal differentiation), who exhibit an eczema like skin condition. They then used these mice to demonstrate the predisposition of such affected individuals to allergic asthma. Occurance of allergic asthma was 7-fold higher in the mutant mouse population, compared to a wild-type population.

The authors then went on to demonstrate that a cytokine called thymic stromal lymphopoietin (TSLP), which is secreted by the damaged skin into the circulation, is required for atopic march in the mutant mice. They show that by knocking out the TSLP receptor in these mice, they can prevent atopic march. They also show that over-production of TSLP in the skin is sufficient to cause allergic asthma, regardless of the cause of that over-production.

This is a paper a little outside my areas of expertise, which is why this is much more of a skim overview than normal. However, there is clearly good work being done here elucidating the molecular mechanisms of a very common disease process. There are also clear implications in this paper on the future management and treatment of eczema and asthma patients. Even though this is unlikely to improve my own experiences of these conditions, I’m very happy this kind of work is being done.

Demehri, S., Morimoto, M., Holtzman, M., & Kopan, R. (2009). Skin-Derived TSLP Triggers Progression from Epidermal-Barrier Defects to Asthma PLoS Biology, 7 (5) DOI: 10.1371/journal.pbio.1000067

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