Interleukin-33 in atopic dermatitis.

• IL-33 is up-regulated in the lesional skin of patients with atopic dermatitis (AD). • The skin-specific expression of IL-33 causes AD-like eczema in mice. • Group 2 innate lymphoid cells (ILC2s) produce type2 cytokines in response to IL-33. • IL-33 promotes itch and disrupts the skin barrier. • Clinical applications of anti-IL-33 (or ST2) antibodies are expected. Atopic dermatitis (AD) is characterized by pruritus, barrier disruption, and inflammationincluding type 2 cytokine production. Interleukin-33 (IL-33) is an inflammatory cytokine that is over-expressed in the keratinocytes of patients with AD. IL-33 transgenic mice, which express IL-33 specifically in keratinocytes, spontaneously develop AD-like eczema, suggesting that IL-33 is sufficient for the development of AD. IL-33 stimulates various cells, including group 2 innate lymphoid cells (ILC2s), to produce type 2 cytokines, such as IL-5 and IL-13, and IL-33-stimulated basophils activate ILC2s via IL-4. ILC2s are enriched in human AD skin lesions, and ILC2 isolated from AD lesions, are activated by IL-33, not by thymic stromal lymphopoietin (TSLP). IL-33 induces IL-31, thereby promoting pruritus and scratching behavior. Conversely, scratching the skin promotes IL-33 release from keratinocytes. IL-33 reduces the expression of filaggrin and claudin-1; it also reduces the skin barrier function. However, barrier destruction causes percutaneous exposure to allergens or IL-33 release. Thus, IL-33 is a common point of entry into the itch–scratch cycle of AD. These new findings can facilitate the development of novel therapeutic drugs targeting IL-33. [ABSTRACT FROM AUTHOR]