Neurotrophins in allergic diseases: from neuronal growth factors to intercellular signaling molecules

Understanding the complex pathophysiology of allergic diseases has been a main challenge of clinical and experimental research for many years. It is well known that the allergic inflammation triggers neuronal dysfunction and structural changes in the diseased tissues such as the airways or the skin. Recent evidence has emerged that the inflammatory response is also controlled by resident tissue cells such as neurons and structural cells. Therefore, signaling molecules that mediate inflammatory interactions among immune, neuronal, and structural cells are becoming a focus of allergy research. Neurotrophins, a family of homologous growth factors initially discovered in the nervous system, display such bidirectional signaling. The expression of neurotrophins, such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), is highly upregulated during allergic inflammation. Neurons, structural cells, and invading immune cells were now identified not only as sources but also as targets of neurotrophins within the inflamed tissue. In this review, we provide an actual overview of the role of neurotrophins in the pathobiology of allergic diseases. We discuss recent findings in human and animal studies such as the regulation of neurotrophin expression during allergic inflammation and the effect of neurotrophins on the development and magnitude of allergic reactions.