Various diseases have been established to be associated with interleukin (IL)-31 signaling in recent years. Firstly, it was seen with processes involving pruritus and following, at least partly, concepts of type 2 inflammation like atopic dermatitis, allergic contact dermatitis, urticaria, mastocytosis, allergic rhinitis and asthma. 

Since IL-31 signaling is involved in the development of itch it may also be involved in the stimulation of sneezing, coughing or bronchial hyperreactivity, which may further also be true for other epithelial surfaces like the gut and conditions such as irritable bowel syndrome. 

STAT1-related regulation of IL-31 receptor A may also connect this pathway to autoimmune conditions like systemic sclerosis, dermatomyositis and lupus erythematosus. 

Some patients encounter severe pruritus but IL-31 signaling in autoimmune inflammation may also promote fibrosis and intensify inflammatory circuits.  

Among autoimmune skin diseases, bullous pemphigoid is interesting as in this; patients conceive autoantibodies against hemidesmosomes (BP180, BP230), eosinophilia, urticarial skin lesions, blisters and suffer from severe pruritus. Several studies have revealed the expression of IL-31 and its receptor in this condition, thus making it a suitable candidate for clinical studies targeting IL-31 signaling. 

IL-31 expression and serum levels have also been investigated in cutaneous T-cell lymphoma patients. Evidence suggests a link between IL-31 and malignant diseases like endometrial carcinoma, lung cancer, myeloproliferative disorders, mastocytosis, cutaneous T-cell lymphoma and follicular B cell lymphoma. 

Collectively, IL-31 is a neuroimmune cytokine and IL-31 receptor A signaling symbolizes a key regulator of inflammation that links immune cells, the nervous system and epithelial tissues.

Source: Nemmer JM, Kuchner M, Datsi A, et al. Interleukin-31 signaling bridges the gap between immune cells, the nervous system and epithelial tissues. Front Med (Lausanne). 2021;8:639097.