IL-31 is crucial for induction of pruritus, but not inflammation, in contact hypersensitivity

Abstract

IL-31, which is a member of the IL-6 family of cytokines, is produced mainly by activated CD4+ T cells, in particular activated Th2 cells, suggesting a contribution to development of type-2 immune responses. IL-31 was reported to be increased in specimens from patients with atopic dermatitis, and IL-31-transgenic mice develop atopic dermatitis-like skin inflammation, which is involved in the pathogenesis of atopic dermatitis. However, the role of IL-31 in development of contact dermatitis/contact hypersensitivity (CHS), which is mediated by hapten-specific T cells, including Th2 cells, is not fully understood. Therefore, we investigated this using IL-31-deficient (Il31−/−) mice, which we newly generated. We demonstrated that the mice showed normal migration and maturation of skin dendritic cells and induction of hapten-specific T cells in the sensitization phase of FITC-induced CHS, and normal induction of local inflammation in the elicitation phase of FITC- and DNFB-induced CHS. On the other hand, those mice showed reduced scratching frequency and duration during FITC- and/or DNFB-induced CHS. Our findings suggest that IL-31 is responsible for pruritus, but not induction of local skin inflammation, during CHS induced by FITC and DNFB.

Proactive maintenance therapy of canine atopic dermatitis with the anti‐IL‐31 lokivetmab. Can a monoclonal antibody blocking a single cytokine prevent allergy flares?

“…Finally, our results mirror those seen when inducing allergic contact dermatitis in IL‐31‐deficient ( Il31 −/− ) mice . In this model as in ours, whereas the allergic pruritus was reduced after hapten application, the local skin inflammation was not …”

“…In that study of atopic mice, the mean dermatitis score continued to increase despite repeated treatment with the anti‐IL‐31 mAb every fifth day for seven weeks, thereby corroborating the relative lack of importance of IL‐31 in atopic skin inflammation . Finally, our results mirror those seen when inducing allergic contact dermatitis in IL‐31‐deficient ( Il31 −/− ) mice . In this model as in ours, whereas the allergic pruritus was reduced after hapten application, the local skin inflammation was not …”

Pruritus in ordinary scabies: IL‐31 from macrophages induced by overexpression of thymic stromal lymphopoietin and periostin

“…Although the main cellular source of IL‐31 is considered as activated Th2 cells, monocytes/macrophages, mast cells, eosinophils, and basophils are also able to produce IL‐31. In scabies lesions, we observed a large number of CD68(+) cells in the dermis (Figure A).…”

Biological Effects of IL-26 on T Cell–Mediated Skin Inflammation, Including Psoriasis

“…Finally, to determine whether the effect of IL-26 on angiogenesis and inflammation is specific for the IMQ-induced psoriasis model or can be commonly observed in other types of inflammatory models, we evaluated the role of IL-26 in the DNFB-induced contact hypersensitivity model (Takamori et al, 2018). Similar to the IMQ-induced psoriasis model, excessive blood vessel formation and vascular invasion were observed in the ear skin of hIL-26Tg mice with DNFB-induced contact hypersensitivity ( Supplementary Figure S6a online).…”