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Functional interaction between sensory neurons and mast cells in the early stage of house dust mite-induced type 2 inflammation and itch: a novel therapeutic target of allergic disease

Cellular & Molecular Immunology volume 17, pages 899–900 (2020)Cite this article

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The pathogenesis of allergies has long been described as the interaction of the environment as well as the genetic susceptibility and immune system of an individual. Allergen sensitization, which involves allergen entry through the disrupted skin barrier, antigen processing, and presentation to the immune system that later induces mast cell activation and the T helper 2 (Th2) immune response, is regarded as the early event in the development of atopic dermatitis (AD). High circulating neuropeptides and nerve growth factors, the presence of neuropeptide-expressing neurons in AD skin lesions, and scratching behavior observed in patients with AD provide evidence that the nervous system also plays a key role in the manifestation of AD.1,2 However, our understanding of nociceptive sensory neurons that reside in the dermis of patients with AD has not been limited to their primary functions in sensing and transmitting pain and itch signals or initiating defensive responses such as scratching and removal. Several groups have unfolded the pathological role of nociceptors and neuropeptides in regulating AD-related innate lymphoid cell 2 in allergic inflammation.3,4 The interaction between the nervous system and immune cells was also reported in fungal-infected skin inflammation and psoriasis but not in AD.5,6 Serhan et al., for the first time, revealed the detailed mechanism of how allergens trigger peripheral nociceptive sensory neurons to release neuropeptides and eventually signal mast cells in the skin to degranulate and induce Th2 inflammation through a nonhistaminergic itch pathway in the early stage of AD development.7

House dust mites (HDMs) are the most potent indoor allergens and are associated with the manifestation of AD. HDMs can be taken up through the skin in various ways. Epithelial cells or dendritic cells can capture HDM proteases via protease-activated receptors and pattern-recognition receptors. HDMs can also enter via the disruption of the tight junctions and transmembrane adhesion molecules of epithelial cells by their proteolytic activities.8 The entered antigen is then presented to antigen-presenting cells, mainly dendritic cells, to signal downstream inflammatory responses in various allergic diseases. Along with HDM, bacterial Staphylococcus aureus (S. aureus) colonization on the skin is commonly found on the skin lesions of individuals with AD. Acute infection of S. aureus directly activates nociceptors to release neuropeptides, which modulate the local inflammatory response.9 Nevertheless, whether the Th2-related allergen HDM possesses a similar capacity in signaling nociceptors to induce neuropeptides for the downstream inflammatory response in AD is unclear.

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Authors and Affiliations

  1. Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, China

    Miranda Sin-Man Tsang & Chun Kwok Wong

  2. Institute of Chinese Medicine and State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Hong Kong, China

    Miranda Sin-Man Tsang & Chun Kwok Wong

  3. Li Dak Sum Yip Yio Chin R & D Centre for Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China

    Chun Kwok Wong

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  1. Miranda Sin-Man Tsang
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  2. Chun Kwok Wong
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Correspondence to Chun Kwok Wong.

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Tsang, M.SM., Wong, C.K. Functional interaction between sensory neurons and mast cells in the early stage of house dust mite-induced type 2 inflammation and itch: a novel therapeutic target of allergic disease. Cell Mol Immunol 17, 899–900 (2020). https://doi.org/10.1038/s41423-020-0508-6

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