A modular view of cytokine networks in atopic dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disease known for its complex pathophysiology involving several immune pathways. In the lesion, signals from barrier disruption, allergens, and microbial colonization are integrated and transmitted to diverse immune cell types, which initiate and maintain the disease. Cytokines are critical in the allergic intercellular communication networks. This review focuses on up-to-date knowledge on the role of cytokines in AD, including recently described functions as well as novel cellular sources. We propose three modules defined as the cellular source of groups of cytokines: (1) keratinocytes, (2) innate immune cells, and (3) T cells. This view enables to better position the function of novel cytokine players, such as thymic stromal lymphopoetin, IL-21, IL-25, and IL-33, in linking different modules and ultimately leading to the allergic inflammatory phenotype. Persistent efforts in the detailed characterization of cytokine networks will be fundamental for the understanding of the complex pathogenic mechanisms of the disease and for guiding targeted therapeutic interventions.