IL‐31 and IL‐31 receptor alpha in pemphigus: Contributors to more than just itch?

Abstract

Pemphigus is an autoimmune blistering disorder with four major subtypes: pemphigus vulgaris (PV), pemphigus vegetans (PVe), pemphigus foliaceus (PF), and pemphigus herpetiformis (PH). Among them, PF and PH present itching as a clinical feature; however, the mechanisms behind the pruritus are still unclear. In this report, we sought to investigate the expression of a type 2 inflammation‐related pruritogenic cytokine IL‐31 and its receptor subunit IL‐31RA through immunofluorescence staining analysis. The number of eosinophils, basophils, and mast cells, and the expression levels of thymic stromal lymphopoietin (TSLP) and periostin were also investigated. Evaluation showed an increase in the number of dermal IL‐31+ cells and IL‐31RA+ cells in PH and PVe. Epidermal expression of IL‐31RA increased in PV, PF, and PVe, but not in PH, compared to healthy individuals. The number of dermal eosinophils and basophils was also increased in PVe and PH. The number of dermal mast cells and expression levels of TSLP and periostin did not change among pemphigus subtypes and healthy controls. Collectively, enhanced IL‐31/IL‐31RA signaling and the increased numbers of dermal eosinophils and basophils may participate in itching in PH. On the other hand, IL‐31/IL‐31RA signaling seemed unable to provoke itching in PVe, a non‐pruritic subtype of pemphigus, although it might contribute to epidermal thickening and dermal fibrosis.

In chronic spontaneous urticaria, IgE and C‐reactive protein are linked to distinct microRNAs and interleukin‐31

“…63 Furthermore, elevated IL-31 levels have been reported in autoimmune diseases such as psoriasis, 64 systemic lupus erythematosus, 65 dermatomyositis, 66 bullous pemphigoid, 67 and subtypes of pemphigus including the non-pruritic subtype pemphigus vegetans. 68 IL-31 levels were previously reported to be elevated in CSU, but its role in the pathogenesis has not been clarified yet. 20,23,69 The decrease in IL-31 levels after omalizumab treatment in CSU patients suggests that IL-31 is a pathogenic driver of CSU.…”

“…Not surprisingly, IL‐31 levels are elevated in pruritic diseases such as atopic dermatitis, 19 prurigo nodularis, 61 lichen planus, 62 and uremic pruritus 63 . Furthermore, elevated IL‐31 levels have been reported in autoimmune diseases such as psoriasis, 64 systemic lupus erythematosus, 65 dermatomyositis, 66 bullous pemphigoid, 67 and subtypes of pemphigus including the non‐pruritic subtype pemphigus vegetans 68 …”

“… 63 Furthermore, elevated IL‐31 levels have been reported in autoimmune diseases such as psoriasis, 64 systemic lupus erythematosus, 65 dermatomyositis, 66 bullous pemphigoid, 67 and subtypes of pemphigus including the non‐pruritic subtype pemphigus vegetans. 68 …”

Possible Association of Interleukin-31/-31RA Signalling and Basophils with Itch in Porokeratosis

“…IL-31 is reported to stimulate the epidermal keratinocytes to secrete some pruritogens, including leukotriene B4 and thromboxane A2 ( 5 , 9 ). A recent study has suggested that IL-31/IL-31RA signalling in the epidermis contributes not only to itching but also to the abnormal epidermal differentiation process ( 10 ). Characteristic findings of the epidermis in porokeratosis may be associated with IL-31/IL-31RA signalling.…”