IgG from Adult Atopic Dermatitis (AD) Patients Induces Thymic IL-22 Production and CLA Expression on CD4+T Cells: Possible Epigenetic Implications Mediated by miRNA

Author(s)

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

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 23, n. 12, p. 18-pg., 2022-06-01.

Abstract

Atopic dermatitis (AD) is a common relapsing inflammatory skin disorder characterized by immune-mediated inflammation and epidermal barrier dysfunction. The pathogenesis of AD is multifactorial and has not been fully elucidated to date. This study aimed to evaluate whether serum IgG from adult AD patients could modulate the thymic maturation of IL-22-producing T cells and CLA+ T cells of non-atopic infants. Given that miRNAs regulate immune response genes, we evaluated whether miRNA expression is also altered in cultured thymocytes. Thymocytes were cultured with purified IgG from AD patients or control conditions (mock, Intravenous-IgG (IVIg), non-atopic IgG, or atopic non-AD IgG). Using flow cytometry analysis, we assessed the expression of CLA and intracellular levels of IL-4, IFN-gamma, and IL-22 on double-positive T cells (DP T), CD4 T cells, or CD8 T cells. We also investigated the frequency of IgG isotypes and their direct interaction with the thymic T cells membrane. The miRNA profiles were evaluated by the Illumina small RNA-seq approach. MiRNA target gene prediction and enrichment analyses were performed using bioinformatics. Increased frequencies of IL-22 and CLA+ producing CD4+ T cells cultured with IgG of AD patients was seen in non-atopic infant thymocytes compared to all control conditions. No alterations were observed in the frequency of IgG isotypes among evaluated IgG pools. Evidence for a direct interaction between IgG and thymic DP T, CD4 T, and CD8 T cells is presented. The small RNA-seq analysis identified ten mature miRNAs that were modulated by AD IgG compared to mock condition (miR-181b-5p, hsa-miR-130b-3p, hsa-miR-26a-5p, hsa-miR-4497, has-miR-146a, hsa-let-7i-5p, hsa-miR-342-3p, has-miR-148a-3p, has-miR-92a and has-miR-4492). The prediction of the targetome of the seven dysregulated miRNAs between AD and mock control revealed 122 putative targets, and functional and pathway enrichment analyses were performed. Our results enhance our understanding of the mechanism by which IgG can collaborate in thymic T cells in the setting of infant AD. (AU)

• FAPESP's process: 18/08631-3 - Bacterial Community Composition and Diversity in Billing Reservoir Examined by Massive Paralelel Sequence Analysis of 16S rRNA Genes
• Grantee: Sabri Saeed Mohammed Ahmed Al-Sanabani
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/09741-0 - Analysis of the modulating effect of IgG antibodies from atopic individuals to the mite Dermatophagoides pteronyssiunus on the maturation and cytokine production of human intrathymic lymphocytes
• Grantee: Thamires Rodrigues de Sousa
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 18/05181-7 - Translational evaluation of IgG effect upon the maturation of offspring thymus derived TCD4, TCD8, nTreg, gammadeltaT and e B cells.
• Grantee: Alberto José da Silva Duarte
• Support Opportunities: Regular Research Grants