House dust mite allergy exacerbates psoriasis by promoting hyperactivation of mast cells and Th17 cells

Accumulating evidence has linked environmental factors, such as allergens, to the exacerbation of psoriasis through effects on immune responses. This study assessed the impact of house dust mite (HDM) allergy-one of the most prevalent allergens-on the severity of psoriasis using retrospective patient analyses and experimental models. Clinically, patients with allergies demonstrated significantly increased psoriasis severity, as determined by medication usage. In vitro, HaCaT cells co-stimulated with interleukin (IL)-17A and histamine exhibited synergistically elevated production of pro-inflammatory cytokines IL-6 and Il36g via the activation of the MAPK/NF-κB signaling pathway, as confirmed by ELISA and immunoblotting. Additionally, the co-stimulation increased IL-17RA expression, as confirmed by immunoblotting. In vivo, C57BL/6 mice sensitized and challenged with HDM were subsequently treated with imiquimod (IMQ) to induce psoriasis-like dermatitis, resulting in aggravated psoriatic phenotypes as evidenced by higher Psoriasis Severity Index (PSI) scores and increased epidermal thickness observed in skin biopsies. These effects were associated with enhanced differentiation and activation of T-helper (Th)2 and Th17 cells, as revealed by flow cytometry, as well as increased mast cell activation in skin biopsies, indicating an amplified inflammatory response driven by HDM allergy. These findings underline the role of HDM allergy in intensifying psoriasis, mediated by complex immune interactions involving Th17 cells and mast cells, suggesting managing environmental allergens and targeting these pathways could offer potential strategies to mitigate the severity of psoriasis.