Explore the vast range of titles available.

Allergic contact dermatitis (ACD) is a cutaneous inflammatory disorder mediated by allergen-specific memory T cells. Methylisothiazolinone (MI), a preservative widely used in industrial and cosmetic products and a component of Kathon CG, has led to a substantial rise in ACD cases. Despite increasing sensitization rates, the innate immune mechanisms and transcriptional responses induced by MI in the skin remain poorly understood. Individuals with positive patch tests exclusively to MI were recruited at the Contact Dermatitis Clinic of Hospital das Clínicas (São Paulo). Participants were re-exposed to MI or saline, and skin biopsies were collected 48 hours later. Healthy MI-negative controls were also exposed to MI and saline. Histopathology and RNA-sequencing were performed. Differentially expressed genes (DEGs) were analyzed, and key findings were validated by qPCR and protein expression of IL-9 and IL-24. Two distinct MI-responsive groups emerged among ACD patients:ACD-A (high responders): pronounced histopathology (spongiosis, microvesicles). ACD-B (low responders): milder reactions with absence of spongiosis. In ACD-A, MI exposure resulted in 1,588 upregulated and 2,090 downregulated genes compared to ACD-B. DEGs were enriched for innate immune and inflammatory pathways, including IL-24, IL-9, IL-13, and NTRK1 (upregulated), while IL-37 and IL-18 were downregulated. Compared to MI-negative ACD controls, ACD-A showed 1,169 upregulated and 321 downregulated genes. qPCR confirmed increased NTRK1 and IL-9 expression and reduced IL-18 levels. IL-9 and IL-24 protein levels were higher in the dermal layer of ACD-A. MI-sensitized individuals exhibit heterogeneous innate immune responses despite uniformly positive patch tests. IL-9, IL-24, and NTRK1 appear to play important roles in the heightened inflammatory response observed in high-responder individuals, while downregulation of IL-18 and IL-37 may contribute to impaired regulatory pathways. These findings highlight previously undescribed heterogeneity in MI-induced ACD and identify potential targets for better understanding disease pathogenesis.

Chronic urticaria (CU) is a skin disease characterized by recurrent episodes of urticaria and/or angioedema, persisting for more than six weeks. Chronic urticaria is classified as chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU). Histamine, released by mast cells and basophils, is the central mediator in the development of signs and symptoms, especially pruritus. IL-31 activates pruritus via IL-31RA. Th2 cytokines also contributes to the inflammatory environment, releasing further IL-31. We aimed to investigate the quantification of mast cells, expression of pro-inflammatory cytokines in skin samples from individuals with CU and cell activation by the basophil activation test. Thirteen patients with CSU, 11 patients with CIndU and 10 healthy controls (HC) were enrolled in the study. We performed histologic quantification of the mast cells, metachromatic stained with toluidine blue, in CSU and CIndU lesional samples; IL-31, IL-31RA, IL-4 and IFN-γ expression by immunohistochemistry; and basophil activation test (BAT) by flow cytometry. The main findings were increased mast cell quantification in CSU; increased epidermal and dermal expression of IL-31 in CSU lesional samples and increased dermal expression in CIndU samples; augmented IL-31RA expression at epidermis and dermis of CSU group; augmented expression IL-4 at epidermis of CSU patients. We also found enhanced BAT positivity in CSU, reinforcing the autoimmune profile of our CSU patients. The analysis of the proinflammatory cytokines related to pruritus, showed increased expression of the evaluated components. These remarkable findings in CSU emphasize their relevance as potential disease biomarkers and targets for immunomodulatory interventions.