IgG from Adult Atopic Dermatitis (AD) Patients Induces Nonatopic Neonatal Thymic Gamma-Delta T Cells (gamma delta T) to Acquire IL-22/IL-17 Secretion Profile with Skin-Homing Properties and Epigenetic Implications Mediated by miRNA

Autor(es)

Fagundes, Beatriz Oliveira ; de Sousa, Thamires Rodrigues ; Nascimento, Andrezza ; Fernandes, Lorena Abreu ; Sgnotto, Fabio da Ressureicao ; Orfali, Raquel Leao ; Aoki, Valeria ; Duarte, Alberto Jose da Silva ; Sanabani, Sabri Saeed ; Victor, Jefferson Russo

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 23, n. 12, p. 16-pg., 2022-06-01.

Resumo

gamma delta T cells mature in the human thymus, and mainly produce IL-17A or IFN-gamma, but can also produce IL-22 and modulate a variety of immune responses. Here, we aimed to evaluate whether IgG from AD patients (AD IgG) can functionally modulate thymic nonatopic gamma delta T cells. Thymic tissues were obtained from 12 infants who had not had an atopic history. Thymocytes were cultured in mock condition, or in the presence of either AD IgG or therapeutic intravenous IgG (IVIg). Following these treatments, intracellular cytokine production, phenotype, and microRNA expression profiles were investigated. AD IgG could downregulate alpha 4 beta 7, upregulate CLA, and induce the production of IFN-gamma, IL-17, and IL-22 in gamma delta T cells. Although both AD IgG and IVIg could directly interact with gamma delta T cell membranes, AD IgG could reduce gamma delta T cell apoptosis. AD IgG could upregulate nine miRNAs compared to IVIg, and six when compared to the mock condition. In parallel, some miRNAs were downregulated. Target gene prediction and functional analysis indicated that some target genes were enriched in the negative regulation of cellular transcription. This study shows that AD IgG influences the production of IL-17 and IL-22 by intrathymic nonatopic gamma delta T cells, and demonstrates epigenetic implications mediated by miRNAs. (AU)

• Processo FAPESP: 18/05181-7 - Avaliação translacional do efeito modulador e/ou regulador dos anticorpos IgG na maturação de linfócitos TCD4, TCD8, nTreg, Tgammadelta e B intra-tímicos de neonatos.
• Beneficiário: Alberto José da Silva Duarte
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/08631-3 - Composição e diversidade da comunidade bacteriana no reservatório de Billings através do sequenciamento de nova geração do gene 16S rRNA
• Beneficiário: Sabri Saeed Mohammed Ahmed Al-Sanabani
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 19/09741-0 - Análise do efeito modulador dos anticorpos IgG de indivíduos atópicos ao ácaro Dermatophagoides pteronyssiunus na maturação e produção de citocinas de linfócitos intratímicos humanos
• Beneficiário: Thamires Rodrigues de Sousa
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica