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BackgroundNeurotrophin 3 (NT-3) is a member of the neurotrophin family, a group of related proteins that are known to regulate neuro-immune interactions in allergic diseases. Their cellular sources and role in the recruitment of mast cell precursors in atopic dermatitis have not been characterized in detail so far.ObjectiveCharacterize NT-3 on a transcriptional and translational level in individuals with atopic dermatitis with special focus on mast cells.MethodsTo meet this objective NT-3 levels in the serum of AD patients were measured, the effect of NT-3 on keratinocytes was evaluated and the gene expression and regulation assessed using ELISA, immunohistochemistry and RNA quantification.ResultsSystemic levels of NT-3 were found to be higher in individuals with AD as compared to healthy controls. A distinct genetic expression was found in the various cells of the skin. In lesional mast cells of individuals with atopic dermatitis an increased amount of NT-3 was apparent. Functional in vitro experiments demonstrated that NT-3 stimulation led to a suppression of IL-8 secretion by HaCat cells.ConclusionThese findings could imply a role for NT-3 in the pathogenesis of allergic skin diseases.

The demonstration of a decreased level of BDNF gene transcription in lesional MCs points to a differential regulation of MC-released neutrotrophins in cutaneous allergic inflammation. Topically administered neurotrophin receptor-modulating compounds should be receptor target specific and not universally acting in diseases such as atopic dermatitis or allergic asthma.