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

Autor(es)

Orfali, Raquel Leao ^[1] ; Yamada Yoshikawa, Fabio Seiti ^[1] ; da Silva Oliveira, Luanda Mara ^[1] ; Pereira, Natalli Zanete ^[1] ; de Lima, Josenilson Feitosa ^[1] ; Leuzzi Ramos, Yasmim Alefe ^[1] ; da Silva Duarte, Alberto Jose ^[1] ; Sato, Maria Notomi ^[1] ; Aoki, Valeria ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med FMUSP, Lab Dermatol & Immunodeficiencies LIM 56, Dept Dermatol, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 9, SEP 11 2019.
• Citações Web of Science: 0

Resumo

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-gamma, and MIP-1 beta) 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. (AU)

• Processo FAPESP: 16/24161-1 - Caracterização proteômica de exossomas do plasma e de fibroblastos dérmicos na dermatite atópica do adulto
• Beneficiário: Raquel Leão Orfali
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/25645-7 - Avaliação fenotípica e funcional de células dendríticas inflamatórias e de células T na dermatite atópica do adulto
• Beneficiário: Valeria Aoki
• Modalidade de apoio: Auxílio à Pesquisa - Regular