Novel pathogenesis of atopic dermatitis from the view of cytokines in mice and humans.

Type 2 immunity and inflammation underlie allergic skin disorders, such as atopic dermatitis (AD). In type 2 inflammation, IL-4, IL-13, and IL-5, which are signature type 2 cytokines, are mainly produced by type 2 helper T (Th2) cells and form the characteristic features of AD. Epithelial cell-derived cytokines such as IL-25, IL-33, and TSLP initiate type 2 inflammation by modulating various cells, including group 2 innate lymphoid cells. Moreover, IL-31, a newly identified type 2 cytokine produced mainly by Th2 cells, induces pruritus by acting on sensory neurons in the skin. Based on both basic and clinical findings, several biologics targeting Th2 cytokines have been developed and exhibited significant efficacy as therapeutic reagents for AD. We have summarized the roles of each cytokine (IL-4, 5, 13, 25, 31, and 33, and TSLP) in the development of type 2 inflammation, especially AD, from the view of basic studies in mice and clinical trials/observation in humans.