Neurotrophins in allergic disease of skin and lung: modulators of immunological and neuronal plasticity

Allergies are chronic inflammatory disease of the skin, lung and gut. Atopic dermatitis represents the main manifestation of the skin, and bronchial asthma is the leading condition in the lower respiratory tract. Both conditions are due to an inappropriate immune response to harmless environmental antigens (or allergens). There is growing evidence for a close interaction between the immune and nervous system in the pathophysiology of allergies. Recent evidence from our group indicates that neurotrophin production including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are elevated in those organs. Both, residential cells including airway epithelium and migratory cells including macrophages, T cells and eosinophils serve as important sources. The effects of increased neurotrophin production are bidirectional. On the one hand, they control sensory nerve fibres in terms of function, neuropeptide synthesis and survival. On the other side, neurotrophins also serve as important survival factors particularly for inflammatory cells such as eosinophils, T cells and macrophages. Utilizing the model of segmental allergen provocation of mild to moderate asthmatic patients, it has been shown that neurotrophins prevent sufficiently apoptotic cell death of lung, but not blood eosinophils. In addition, they augment the ongoing inflammatory reaction. The functional interaction between neurotrophins and immune and nerve cells has been extensively studied in both human and mouse models of experimental allergic asthma. In the latter system, the crucial role of the pan-neurotrophin receptor p75 has been investigated in p75 NTR–/– mice. Furthermore, NGF transgenic animals have been utilized to assess the contribution of NGF. The role of BDNF on differentiation and function of B-lymphocytes has been identified in BDNF–/– mice. In conclusion, our data support the concept that neurotrophins mediate immunological and neuronal plasticity within the neuro-immune network of allergic disease in the lung and skin.