Role of Epithelium-Derived Cytokines in Atopic Dermatitis and Psoriasis: Evidence and Therapeutic Perspectives

Abstract

Atopic dermatitis and psoriasis are two of the most common chronic skin conditions. Current target therapies represent viable and safe solutions for the most severe cases of these two dermatoses but, presently, several limitations exist in terms of efficacy and side effects. A new class of products, epithelium-derived cytokines (TSLP, IL-25, IL-33), show an increasing potential for use in target therapy for these patients, and demonstrate a direct link between a generalized inflammatory and oxidative stress status and the human skin. A review was conducted to better understand their role in the aforementioned conditions. Of these three molecules, TSLP led has been most often considered in studies regarding target therapies, and most of the results in the literature are related to this cytokine. These three cytokines share common stimuli and are linked to each other in both acute and chronic phases of these diseases, and have been challenged as target therapies or biomarkers of disease activity. The results lead to the conclusion that epithelium-derived cytokines could represent a therapeutic opportunity for these patients, especially in itch control. Furthermore, they might work better when paired together with currently available therapies or in combination with in-development treatments. Further studies are needed in order to verify the efficacy and safety of the biologic treatments currently under development.

Insight Into Biological Targets and Molecular Mechanisms in the Treatment of Arsenic-Related Dermatitis With Vitamin A via Integrated in silico Approach

“…Cytokines have been proven to possess pro-inflammation and immunodepression actions. Cytokines have developed promptly, leading to the induction of dermatitis ( 29 ). Previous evidence has suggested that As impacts the production of inflammatory cytokines in the skin, causing allergic dermatitis ( 30 ).…”

New insight of itch mediators and proinflammatory cytokines in epidermolysis bullosa

“…Recently, epithelial cell-derived TSLP has attracted much attention as cytokines that induce allergic immune responses. 32 TSLP is released by primary epithelial cells in response to certain microbial products, physical injury, or inflammatory cytokines. 33 Although the results of this study did not show a trend toward higher TSLP levels in patients with higher BSA indicated by the red dots in Figure 1D, it may be that TSLP is more likely to be produced by epidermal keratinocytes in patients with EB who often have chronic wounds prone to infection and cutaneous dysbiosis.…”

“…TSLP is an epithelial cell‐derived immunostimulatory factor that activates immune cells such as dendritic cells, T cells, and mast cells. Recently, epithelial cell‐derived TSLP has attracted much attention as cytokines that induce allergic immune responses 32 . TSLP is released by primary epithelial cells in response to certain microbial products, physical injury, or inflammatory cytokines 33 .…”

Metabolic Comorbidities in Pediatric Atopic Dermatitis: A Narrative Review

“…However, recently this scenario was further complicated by the discovery of new cytokines involved in Th2 immunity, as epithelium-derived cytokines, namely, Interleukin 25 (IL-25), interleukin 33 (IL-33) and Thymic Stromal Lymphopoietin (TSLP), which have demonstrated to trigger Th2 immunity in response to external stimuli on skin [ 24 , 25 ]. Anyway, the relationship between these new mediators of Th2 response and adipokines has not been fully understood.…”