Dermatophagoides farinae Extract Induces Interleukin 33-Mediated Atopic Skin Inflammation via Activation of RIP1.

Receptor-interacting protein kinase (RIP) family 1 signaling has complex effects on inflammatory processes and cell death, but little is known concerning allergic skin diseases. We examined the role of RIP1 in Dermatophagoides farinae extract (DFE)-induced atopic dermatitis (AD)-like skin inflammation. RIP1 phosphorylation was increased in HKCs treated with DFE. Nectostatin-1, a selective and potent allosteric inhibitor of RIP1, inhibited AD-like skin inflammation and the expression of histamine, total IgE, DFE-specific IgE, IL-4, IL-5, and IL-13 in an AD-like mouse model. The expression of RIP1 was increased in ear skin tissue from a DFE-induced mouse model with AD-like skin lesions and in the lesional skin of AD patients with high house dust mite sensitization. The expression of IL-33 was down-regulated after RIP1 inhibition, and the levels of IL-33 were increased by over-expression of RIP1 in keratinocytes stimulated with DFE. Nectostatin-1 reduced IL-33 expression in vitro and in the DFE-induced mouse model. These results suggest that RIP1 can be one of the mediators that regulate IL-33-mediated atopic skin inflammation by house dust mites.

Effect of COVID-19 (SARS-CoV-2) Vaccination on Patients with Atopic Dermatitis Treated with Dupilumab: A Multicenter, Observational Study.

BACKGROUND: Atopic dermatitis (AD) patients usually wonder if their condition will worsen after vaccination or if they should continue with the treatment they are receiving. Considering that many patients treated with dupilumab had previously experienced severe AD symptoms and flares, the concerns are more understandable. OBJECTIVE: This study aimed to investigate the safety of the coronavirus disease 2019 (COVID-19) vaccination in patients with AD treated with dupilumab. METHODS: We enrolled 133 patients (101 dupilumab-treated and 32 systemic oral agents-treated as control group) with AD from six hospitals. Patients were asked about worsening pruritus and AD (5-point Likert scale) after vaccination. AD variables (eczema area and severity index [EASI], investigator's global assessment [IGA], itch numerical rating scale [NRS], sleep NRS, and patient-oriented eczema measure [POEM]) were compared pre- and post-vaccination. Adverse reactions to the COVID-19 vaccination were observed. RESULTS: The incidence of adverse reactions to COVID-19 vaccines and worsening AD symptoms in dupilumab-treated patients were not significantly different compared with that in the control group. The itch NRS score increased significantly after vaccination (p<0.001). However, there were no statistically significant differences between the pre-and post-EASI, IGA, and POEM scores. Eight patients (7.9%) had worse EASI scores and required rescue therapy; however, most were easily managed with low-dose steroids or topical agents. None of the patients discontinued dupilumab treatment. CONCLUSION: No serious adverse reactions were observed in patients with AD after COVID-19 vaccination. Exacerbation of pruritus and AD symptoms was observed but was mostly mild and transient.

Preventative Effects of Antioxidants against PM10 on Serum IgE Concentration, Mast Cell Counts, Inflammatory Cytokines, and Keratinocyte Differentiation Markers in DNCB-Induced Atopic Dermatitis Mouse Model.

Particulate matter (PM) can cause oxidative stress, inflammation, and skin aging. We investigated the effects of antioxidants such as dieckol, punicalagin, epigallocatechin gallate (EGCG), resveratrol, and Siegesbeckiae Herba extract (SHE) against PM < 10 µm (PM10) on serum IgE concentration, mast cell counts, inflammatory cytokines, and keratinocyte differentiation markers in a 2,4-Dinitrochlorobenzene (DNCB)-induced atopic dermatitis mouse model. Seven-week-old BALB/c mice were sensitized with 2% DNCB. Atopic dermatitis-like lesions were induced on the mice with 0.2% DNCB. Antioxidants and PM10 were applied to the mice for 4 weeks. PM10 increased the serum IgE concentration and spleen weight in mice, and all antioxidants downregulated these parameters. Histological examination showed an increase in epidermal thickness and mast cell counts in response to PM10, and all antioxidants showed a decrease. PM10 upregulates the expression of inflammatory cytokines, including interleukin (IL)-1ß, IL-4, IL-6, IL-17α, IL-25, IL-31 and thymic stromal lymphopoietin (TSLP) in mice, and all antioxidants inhibited the upregulation of inflammatory cytokines. ELISA showed the same results as real-time PCR. PM10 downregulates the expression of keratinocyte differentiation markers, including loricrin and filaggrin, in mouse keratinocytes and antioxidants prevented the downregulation of the keratinocyte differentiation markers. Conclusively, PM10 aggravated the DNCB-induced mouse model in serum IgE concentration, mast cell counts, inflammatory cytokine, and keratinocyte differentiation markers. In addition, antioxidants modulated changes in the DNCB-induced mouse model caused by PM10.