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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.
Int J Mol Sci. 2022 Jun 20; 23(12)IJ

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-γ, 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.

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Authors+Show Affiliations

de Sousa TR
Laboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of Sao Paulo, Av. Dr. Enéas Carvalho de Aguiar 500, Sao Paulo 05403-000, Brazil.
Fagundes BO
Laboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of Sao Paulo, Av. Dr. Enéas Carvalho de Aguiar 500, Sao Paulo 05403-000, Brazil.
Nascimento A
Post-Graduation Program in Translational Medicine, Federal University of São Paulo, Sao Paulo 04039-002, Brazil.
Fernandes LA
Post-Graduation Program in Translational Medicine, Federal University of São Paulo, Sao Paulo 04039-002, Brazil.
Sgnotto FDR
Division of Hematology, Medical School, University of Sao Paulo, Sao Paulo 01246-000, Brazil.
Orfali RL
Laboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of Sao Paulo, Av. Dr. Enéas Carvalho de Aguiar 500, Sao Paulo 05403-000, Brazil.
Aoki V
Laboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of Sao Paulo, Av. Dr. Enéas Carvalho de Aguiar 500, Sao Paulo 05403-000, Brazil.
Duarte AJDS
Laboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of Sao Paulo, Av. Dr. Enéas Carvalho de Aguiar 500, Sao Paulo 05403-000, Brazil. Division of Pathology, Medical School, University of Sao Paulo, Sao Paulo 05403-000, Brazil.
Sanabani SS
Laboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of Sao Paulo, Av. Dr. Enéas Carvalho de Aguiar 500, Sao Paulo 05403-000, Brazil. Laboratory of Medical Investigation LIM-03, Division of Pathology, Medical School, University of Sao Paulo, Sao Paulo 05403-000, Brazil.
Victor JR
Laboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of Sao Paulo, Av. Dr. Enéas Carvalho de Aguiar 500, Sao Paulo 05403-000, Brazil. Faculdades Metropolitanas Unidas (FMU), Health Sciences School, Sao Paulo 04505-002, Brazil. Medical School, Universidade Santo Amaro (UNISA), Sao Paulo 04829-300, Brazil.

MeSH

AdultCD4-Positive T-LymphocytesDermatitis, AtopicEpigenesis, GeneticHumansImmunoglobulin GInterleukinsMicroRNAs

Pub Type(s)

Journal Article

Language

eng

PubMed ID

35743308

Citation

de Sousa, Thamires Rodrigues, et al. "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." International Journal of Molecular Sciences, vol. 23, no. 12, 2022.
de Sousa TR, Fagundes BO, Nascimento A, et al. 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. Int J Mol Sci. 2022;23(12).
de Sousa, T. R., Fagundes, B. O., Nascimento, A., Fernandes, L. A., Sgnotto, F. D. R., Orfali, R. L., Aoki, V., Duarte, A. J. D. S., Sanabani, S. S., & Victor, J. R. (2022). 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. International Journal of Molecular Sciences, 23(12). https://doi.org/10.3390/ijms23126867
de Sousa TR, et al. 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. Int J Mol Sci. 2022 Jun 20;23(12) PubMed PMID: 35743308.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - de Sousa,Thamires Rodrigues, AU - Fagundes,Beatriz Oliveira, AU - Nascimento,Andrezza, AU - Fernandes,Lorena Abreu, AU - Sgnotto,Fábio da Ressureição, AU - Orfali,Raquel Leão, AU - Aoki,Valéria, AU - Duarte,Alberto José da Silva, AU - Sanabani,Sabri Saeed, AU - Victor,Jefferson Russo, Y1 - 2022/06/20/ PY - 2022/04/19/received PY - 2022/06/10/revised PY - 2022/06/11/accepted PY - 2022/6/24/entrez PY - 2022/6/25/pubmed PY - 2022/6/28/medline KW - IL-22 KW - Th22 KW - atopic dermatitis KW - human KW - miRNA KW - thymus JF - International journal of molecular sciences JO - Int J Mol Sci VL - 23 IS - 12 N2 - 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-γ, 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. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/35743308/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_ DB - PRIME DP - Unbound Medicine ER -