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Staphylococcus aureus colonizes the skin of atopic dermatitis (AD) individuals, but the impact of its enterotoxins on the chronic activation of CD4⁺ T cells demands further analysis. We aimed to analyze the CD4⁺ T cell anergy profile and their phenotypic and functional features through differential expression of cellular activation markers, cytokine production and response to staphylococcal enterotoxin A (SEA). A panel of 84 genes relevant to T cell anergy was assessed by PCR array in FACS-sorted CD4⁺ T cells, and the most prominent genes were validated by RT-qPCR. We evaluated frequencies of circulating CD4⁺ T cells secreting single or multiple (polyfunctional) cytokines (IL-17A, IL-22, TNF, IFN-γ, and MIP-1β) and expression of activation marker CD38 in response to SEA stimulation by flow cytometry. Our main findings indicated upregulation of anergy-related genes (EGR2 and IL13) promoted by SEA in AD …