Il31, a cytokine, is mainly secreted by immune cells like TH2 cells [2,3]. It is a key player in neuroimmune communication, participating in multiple pathophysiological processes of atopic disorders, especially in driving pruritus in atopic dermatitis (AD) [2]. It exerts its effects through activation of the heterodimeric receptor IL31 receptor A (IL31RA)/Oncostatin M receptor (OSMRβ), which is expressed on dorsal root ganglia neurons, epithelial cells, and innate immune cells [2].

In a mouse model of house dust mite (HDM)-induced allergic dermatitis, Il31 -deficient mice showed less HDM dermatitis-associated scratching, consistent with Il31's role as a pruritogen [1]. However, Il31 deficiency increased the number and proportion of cutaneous type 2 cytokine-producing CD4+ T cells and serum IgE in response to HDM, and selectively enriched Il4ra+ monocytes and macrophages capable of fueling a feedforward type 2 inflammatory loop in HDM dermatitis skin [1]. This indicates that IL-31 is not strictly a pro-inflammatory cytokine but an immunoregulatory factor that limits the magnitude of type 2 inflammatory responses in the skin [1].

In conclusion, Il31 is a crucial cytokine in the context of neuroimmune-mediated itch and inflammation, especially in AD. Mouse models, such as the Il31-deficient mice, have been instrumental in revealing its dual role as a pruritogen and an immunoregulatory factor in allergic dermatitis, contributing to our understanding of the complex pathophysiology of AD and potentially other pruritic skin diseases.