Emerging role of interleukin‐31 and interleukin‐31 receptor in pruritus in atopic dermatitis

Abstract

Atopic dermatitis (AD) is a chronic or chronically relapsing, eczematous, severely pruritic skin disorder associated with skin barrier dysfunction. The lesional skin of AD exhibits T helper 2 (T H 2)-deviated immune reactions. Interleukin-31 (IL-31), preferentially produced from T H 2 cells, is a potent pruritogenic cytokine, and its sys- First-line treatments of AD include the application of emollients for dry skin, topical steroids, and tacrolimus for skin inflammation, followed by second-line adjunct therapies such as systemic cyclosporine, short-term oral steroids, and ultraviolet radiation.

Epithelial barrier dysfunctions in atopic dermatitis: a skin-gut-lung model linking microbiome alteration and immune dysregulation

“…Itch is primarily a sensory perception of the skin, mediated by neuronal fibres, C fibres and Aδ fibres, which relay tactile stimulation through the spinothalamic tract to the thalamus and higher processing centres to modulate itch perception, memory and repetitive scratching behaviour . Although the exact mechanism has not been elucidated, it has been purported that endogenous and exogenous triggers such as histamine, proteases, substance P, various ILs including IL‐31, and environmental allergens can signal through specific itch pathways (such as histamine 1 receptor, protease‐activated receptor 2, neurokinin 1 receptor, IL‐31 receptor, and transient receptor potential cation channel ankyrin subtype 1) present on nerve‐fibre endings . Following breaks in the skin, allergens and pathogens gain entry across the epidermis and activate a Th2 allergic inflammatory response, which increases lymphovascular permeability allowing for the additional recruitment of pruritic initiators to the site of injury.…”

“…IL‐31 is primarily secreted by Th2 T cells following stimulation by IL‐4 and to a lesser extent by dendritic cells, mast cells, eosinophils and basophils (Fig. ) . IL‐31 primarily modulates cell‐mediated immunity in the skin through perception of itch in the peripheral nervous system, in the lung through increased airway inflammation, and in the intestine through defence against microbes .…”

Effects of a ceramide‐containing water‐in‐oil ointment on skin barrier function and allergen penetration in an IL‐31 treated 3D model of the disrupted skin barrier

“…AD lesions exhibit reduced levels of ceramides in the stratum corneum and changes in their relative composition . First‐line treatments of AD include the application of emollients for dry skin . Such emollients aim to prevent water loss from the skin, e.g.…”

The role of phosphodiesterase 4 in the pathophysiology of atopic dermatitis and the perspective for its inhibition

“…Some Th2 and Th22 cytokines have been shown to decrease expression of terminal differentiation genes (ie, filaggrin), which contributes to skin barrier defects . Increased IL‐31 is associated with itch and elongation and branching of IL‐31 receptor A‐positive sensory nerve fibres, and administration of the anti‐IL‐31 receptor A monoclonal antibody nemolizumab to patients with AD resulted in significant reduction in the severity of pruritus compared with placebo . Conversely, IL‐22 mediates epidermal hyperplasia …”