Thymic stromal lymphopoietin‐induced interleukin‐17A is involved in the development of IgE‐mediated atopic dermatitis‐like skin lesions in mice

Abstract

SummaryAtopic dermatitis (AD) is a chronic inflammatory skin disease associated with elevated levels of allergen-specific IgE. Although thymic stromal lymphopoietin (TSLP) and interleukin-17A (IL-17A) have been considered as important factors in allergic diseases, their relationships in AD have not been fully defined. Here, we show the contribution of TSLP-induced IL-17A responses to IgE-mediated AD-like skin lesions. BALB/c mice passively sensitized by intraperitoneal injections of ovalbumin (OVA)-specific IgE monoclonal antibody (mAb) were challenged with OVA applied to the skin six times. Treatment with anti-TSLP mAb during the second to sixth challenges inhibited IgE-mediated AD-like skin lesions and IL-17A production in lymph nodes. Furthermore, the increased number of IL-17A-producing CD4 + and cd T cells in lymph nodes and neutrophilic inflammation in the skin were reduced by anti-TSLP mAb. These findings prompted us to examine the roles of IL-17A. Treatment with anti-IL-17A mAb suppressed the AD-like skin lesions and neutrophilic inflammation; anti-Gr-1 mAb also inhibited them. Furthermore, treatment with CXCR2 antagonist reduced the AD-like skin lesions and neutrophilic inflammation accompanied by the reduction of IL-17A production; the increased CXCR2 expression in the epidermal cells was suppressed by anti-TSLP mAb. Meanwhile, these treatments, except for anti-Gr-1 mAb, inhibited the increased mast cell accumulation in the skin. Collectively, the mechanism of IgE mediating IL-17A-producing CD4 + and cd T cells through TSLP by repeated antigen challenges is involved in AD-like skin lesions associated with skin inflammation, such as neutrophil and mast cell accumulation; TSLP may regulate CXCR2 signalling-induced IL-17A production.

Therapeutic effects of bee venom and its major component, melittin, on atopic dermatitis in vivo and in vitro

“…Th1, Th2, Th17 and Th22). The pathogenesis of acute AD is related to Th2‐dominant inflammation, characterized by the dermal infiltration of Th cells, macrophages and eosinophils, increase in allergen‐specific IgE, mast cell activation and Th2 cytokine production (Mizutani et al ., ). Th2 cells secrete the cytokines IL‐4 and IL‐5, that up‐regulate antibody formation via B cells, eosinophils, mast cells and other pathways (Kidd, ).…”

Toll‐like receptor 4 attenuates a murine model of atopic dermatitis through inhibition of langerin‐positive DCs migration

“…Besides, we evaluated the skin mRNA expression of thymic stromal lymphopoietin (TSLP), a cytokine produced by epithelial cells at barrier surfaces, which is believed to be involved in the development of AD . We found that TSLP production was significantly elevated in TLR4 −/− mice compared with that in WT mice upon DNCB administration (Figure A).…”

“…A lot of studies reveal that imbalance in T helper 1/T helper 2 (Th1/Th2) and defective skin barrier contribute to the pathological mechanism . In AD skin biopsies, the high expression of Th2 cytokines (eg IL‐4, IL‐5 and IL‐13), which in conjunction with other inflammatory mediators, leads to the activation of eosinophils and mast cells, as well as B‐cell switching to pathogenic IgE . Besides, there are two main types of immature skin dendritic cells (DCs): Langerhans cells (LCs) in the epidermis and interstitial (dermal) DCs in the dermis .…”

“…Several studies have documented that activated skin cell‐produced inflammatory cytokines can stimulate the migration of skin DCs to lymph nodes . LCs in the AD patients showed enhanced expression of the high‐affinity receptor for IgE (FcεRI), which accelerate the maturation of LCs in case of binding to IgE …”

A review of the roles of keratinocyte‐derived cytokines and chemokines in the pathogenesis of atopic dermatitis in humans and dogs

“…It was demonstrated that anti‐TSLP antibody inhibited the development of oesophageal eosinophilia and food impaction in a murine model of eosinophilic oesophagitis . In a murine model of AD, treatment with anti‐TSLP antibody inhibited IgE‐mediated AD‐like skin lesions and IL‐17A production in the lymph nodes . In a chronic HDM‐induced asthma model, an anti‐TSLP antibody reversed airway inflammation, prevented structural alterations, and decreased airway hyper‐responsiveness to methacholine and TGF‐beta1 level .…”