1-Minute Summary: 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

The interaction between the nervous system and immune cells has been reported in fungal-infected skin inflammation and psoriasis, but not in atopic dermatitis (AD) [1-3]. Antihistamines are not always effective in treating pruritus in chronic skin inflammation [4].

A recent study by Serhan et al. unraveled how house dust mite allergens can trigger peripheral nociceptive sensory neurons and how these neurons interact with mast cells to degranulate and trigger Th2 inflammation in the early development of AD [5]. This was investigated in a mouse model. Athey found that house dust mite allergens activate Tac1-expressing nociceptive sensory neurons by degrading epithelial junctions by cysteine proteolytic activity. The gene TAC1 encodes the precursor of the neuropeptide substance P. Secreted substance P is taken up by mast cells, triggering the degranulation of mast cells. This induces itch signals and the development of type-2 skin inflammation that resembles human AD symptoms (see Figure) [5].

Intermediate players in the induction of itch and Th2 inflammation may be tryptase and IL-31, both of which can be released by mast cells during degranulation [4]. IL-31 can also activate AD effector cell eosinophils and dermal fibroblasts in vitro, suggesting involvement in Th2-related inflammatory responses [6].

Neuropeptide substance P induces vasodilation, local inflammation, and cellular proliferation in skin that is upregulated in the skin lesions of patients with AD [7,8]. Substance P is also upregulated in the plasma of patients with AD and is positively correlated with their AD severity, suggesting the systemic involvement of substance P in AD [9,10].

The study by Serhan et al. pointed out that substance P might be a promising therapeutic target for the prevention and treatment of AD. The neuron–mast cell cluster identified in their study also indicates a new direction to examine in other allergic disorders [1,4].

Figure: A cluster formed between the nociceptor and mast cell in the skin upon house dust mite activation in the early development of type-2 allergic skin inflammation [1]

 

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