Acute atopic dermatitis and urticaria imprints peripheral monocytes with proinflammatory-prone signature

Background: IL-4 and IL-13, pivotal components of type 2 immunity, have been implicated in inducing trained immunity in myeloid cells. However, the precise inflammatory response of monocytes in individuals with type 2 immune disorders remains uncertain. Objective: To investigate the nuanced inflammatory response of monocytes in patients with type 2 immune disorders, specifically atopic dermatitis and urticaria, upon exposure to LPS stimulation. Methods: We collected peripheral blood mononuclear cells (PBMCs) from patients diagnosed with atopic dermatitis and urticaria. Monocytes were isolated from PBMCs and subjected to targeted LPS stimulation. RNA extraction followed by RNA-seq and ATAC-seq analyses were conducted to elucidate molecular responses. Results: Monocytes from patients with type 2 immune disorders exhibited an augmented inflammatory response upon LPS stimulation. RNA-seq analysis demonstrated significant upregulation of inflammatory cytokines, including IL-6, IL-12, and IL-1b. Moreover, there was a conspicuous enrichment of signaling pathways associated with inflammation. ATAC sequencing revealed heightened chromatin accessibility in patient monocytes, particularly in the promoter regions of inflammatory genes. Conclusion: Our findings unveil an intensified pro-inflammatory response in monocytes following LPS stimulation in type 2 immune disorders such as atopic dermatitis and urticaria. The comprehensive RNA and chromatin analyses underscore the pivotal role of type 2 immune responses in shaping the epigenetically defined inflammatory phenotypes of peripheral monocytes.