Psoriasis is a common inflammatory skin disease. 70-80% of patients with psoriasis also suffer from histamine-independent pruritus. Itch signals are transmitted by dorsal root ganglia nerve fibres innervating the skin. Mast cells have been observed to be more numerous in psoriatic skin, and they release mediators that may influence nerve fibres. The project aimed to observe which type of nerve fibres mast cells could interact with in psoriatic skin, what processes mast cells may contribute to in psoriatic skin, and in what way mediators released by mast cells may influence dorsal root ganglia neurons. Nerve fibres, and specifically substance P-positive nerve fibres, were observed through immunofluorescence to be less frequent in psoriatic lesions compared with non-lesional psoriatic and healthy skin. However, gene set enrichment analysis revealed gene sets related to cell-cell contact and neurons to be enriched, which was supported by the upregulation of genes of the axon attraction and adherens formation pathway, in mast cells from psoriatic lesions compared with mast cells from healthy skin. This may suggest potentially greater interactions between mast cells and nerve fibres in psoriatic lesions. Furthermore, itch-associated genes upregulated in mast cells from psoriatic lesions included genes encoding the mediators tumour necrosis factor-alpha and leukotriene B4, which can also bind to nerve fibres; and so, tumour necrosis factor-alpha and leukotriene B4 may be released by mast cells and interact with nerve fibres to contribute to psoriatic pruritus.
The role of interactions between mast cells and nerve fibres in psoriasis
Atmoko, H. (Author). 31 Dec 2020
Student thesis: Phd