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

doi:10.1016/j.jaci.2005.11.049

Journal of Allergy and Clinical Immunology

Volume 117, Issue 3, March 2006, Pages 583-589

https://doi.org/10.1016/j.jaci.2005.11.049 Get rights and content

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.

Section snippets

Discovery of neurotrophins in allergic diseases

The first observation that neurotrophins may be involved in the pathogenesis of allergic diseases came from studies of patients with vernal keratoconjunctivitis, a disease with local mast cell activation.³ Indeed, NGF was then found to be increased in the blood of patients with various allergic diseases such as allergic asthma, urticaria, and atopic dermatitis.4, 5 In patients with atopic dermatitis, plasma NGF levels correlated positively with inflammatory disease activity.⁵ Intensive research

Neurotrophins and the local nervous system

Neurotrophins control the survival, differentiation, and maintenance of neurons in the peripheral as well as the central nervous system (see review¹). Neurotrophins are target-derived neuronal growth factors that regulate neuronal outgrowth toward their place of synthesis.¹¹ They are essential for the development of the peripheral nervous system and induce a variety of responses in peripheral sensory and sympathetic neurons. These effects include chemotaxis, regulation of neurotransmitter

Neurogenic mechanisms

Structural and functional changes in sensory innervation in the lung or skin are under control of inflammatory mediators, which are released during allergic inflammation. It is well known that various ILs, such as IL-1, mediate signals from the immune to the nervous system and stimulate neuropeptide synthesis.⁴⁵ However, communication between neurons and immune cells is not restricted to these classic cytokines. Recent studies indicate that neurotrophins trigger such neuroimmune interactions as

Conclusion

Blood levels of neurotrophins are increased in allergic diseases such as asthma and atopic dermatitis. There is growing evidence that neurotrophins are part of an integrated adaptive response to several offending stimuli that connect cells of the immune and nervous system together with structural cells. Neurotrophins were initially discovered as growth factors supporting neuronal maintenance, but it is now clear that their target cells are not limited to the nervous system. Tissue and immune

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: Supported by a grant from Deutsche Forschungsgemeinschaft, SFB/TR-22 Projekt A9.

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Mechanisms of asthma and allergic inflammationNeurotrophins in allergic diseases: From neuronal growth factors to intercellular signaling molecules

Section snippets

Discovery of neurotrophins in allergic diseases

Neurotrophins and the local nervous system

Neurogenic mechanisms

Conclusion

Curr Opin Neurobiol

J Neuroimmunol

Regul Pept

J Neuroimmunol

Blood

J Biol Chem

Am J Pathol

J Allergy Clin Immunol

Blood

J Neuroimmunol

Am J Pathol

Eur J Pharmacol

J Invest Dermatol

J Allergy Clin Immunol

Neuroscience

J Invest Dermatol

J Allergy Clin Immunol

J Invest Dermatol

J Dermatol Sci

J Invest Dermatol

J Allergy Clin Immunol

J Biol Chem

J Biol Chem

Physiology of neurotrophins

Annu Rev Neurosci

Increased plasma levels of nerve growth factor in vernal keratoconjunctivitis and relationships to conjunctival mast cells

Invest Opthalmol Vis Sci

Circulating nerve growth factor levels are increased in humans with allergic diseases and asthma

Proc Natl Acad Sci U S A

Nerve growth factor and substance P are useful markers of disease activity in atopic dermatitis

Br J Dermatol

Brain-derived neurotrophic factor is increased in atopic dermatitis and modulates eosinophil functions compared with that seen in nonatopic subjects

J Allergy Clin Immunol

Brain-derived neurotrophic factor in platelets and airflow limitation in asthma

Am J Respir Crit Care Med

The influence of inhalative corticosteroids on circulating nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 in allergic asthmatics

Clin Exp Allergy

Nerve growth factor expression and release in allergic inflammatory disease of the upper airways

Am J Respir Crit Care Med

Neurotrophins are increased in bronchoalveolar lavage fluid after segmental allergen provocation

Am J Respir Crit Care Med

Local and target-derived actions of neurotrophins during peripheral nervous system development

Cell Mol Life Sci

Mechanisms of asthma and allergic inflammation
Neurotrophins in allergic diseases: From neuronal growth factors to intercellular signaling molecules