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Staphylococcal enterotoxins modulate the effector CD4+ T cell response by reshaping the gene expression profile in adults with atopic dermatitis.

Abstract：

: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 patients, associated to a compromised polyfunctional response particularly in CD4+CD38+ T cells in response to antigen stimulation. The pathogenic role of staphylococcal enterotoxins in adult AD can be explained by their ability to downmodulate the activated effector T cell response, altering gene expression profile such as EGR2 induction, and may contribute to negative regulation of polyfunctional CD4+ T cells in these patients.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Orfali RL,Yoshikawa FSY,Oliveira LMDS,Pereira NZ,de Lima JF,Ramos YÁL,Duarte AJDS,Sato MN,Aoki V

doi

10.1038/s41598-019-49421-5

subject

Has Abstract

pub_date

2019-09-11 00:00:00

pages

13082

issue

1

issn

2045-2322

pii

10.1038/s41598-019-49421-5

journal_volume

9

pub_type

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