Dendritic Cells Expressing MyD88 Molecule Are Necessary and Sufficient for CpG-Mediated Inhibition of IgE Production In Vivo
Elevated levels of immunoglobulin E (IgE) are associated with allergies and other immunological disorders. Sensitization with alum adjuvant favours IgE production while CpG-ODN adjuvant, a synthetic toll-like receptor 9 (TLR9) agonist, inhibits it. The cellular mechanisms underlying in vivo TLR regu...
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2019-09-01
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author | Ricardo W. Alberca Custodio Luciana Mirotti Eliane Gomes Fernanda P.B. Nunes Raquel S. Vieira Luís Graça Rafael R. Almeida Niels O. S. Câmara Momtchilo Russo |
author_facet | Ricardo W. Alberca Custodio Luciana Mirotti Eliane Gomes Fernanda P.B. Nunes Raquel S. Vieira Luís Graça Rafael R. Almeida Niels O. S. Câmara Momtchilo Russo |
author_sort | Ricardo W. Alberca Custodio |
collection | DOAJ |
description | Elevated levels of immunoglobulin E (IgE) are associated with allergies and other immunological disorders. Sensitization with alum adjuvant favours IgE production while CpG-ODN adjuvant, a synthetic toll-like receptor 9 (TLR9) agonist, inhibits it. The cellular mechanisms underlying in vivo TLR regulation of immunoglobulin production, specially IgE, are still controversial. Specifically, TLR-mediated IgE regulation in vivo is not yet known. In this study we showed that augmented levels of IgE induced by sensitizations to OVA with or without alum adjuvant or with OVA-pulsed dendritic cells (DCs) were inhibited by co-administration of CpG. Notably, CpG-mediated suppression of IgE production required <i>MyD88</i>-expression on DCs but not on B-cells. This finding contrasts with previous in vitro studies reporting regulation of IgE by a direct action of CpG on B cells via MyD88 pathway. In addition, we showed that CpG also inhibited IgE production in a <i>MyD88</i>-dependent manner when sensitization was performed with OVA-pulsed DCs. Finally, CpG signalling through MyD88 pathway was also necessary and sufficient to prevent anaphylactic antibody production involved in active cutaneous anaphylaxis. |
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issn | 2073-4409 |
language | English |
last_indexed | 2024-03-12T08:20:14Z |
publishDate | 2019-09-01 |
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spelling | doaj.art-e7f309d3295347c5a7bead74e8daa34a2023-09-02T18:34:07ZengMDPI AGCells2073-44092019-09-01810116510.3390/cells8101165cells8101165Dendritic Cells Expressing MyD88 Molecule Are Necessary and Sufficient for CpG-Mediated Inhibition of IgE Production In VivoRicardo W. Alberca Custodio0Luciana Mirotti1Eliane Gomes2Fernanda P.B. Nunes3Raquel S. Vieira4Luís Graça5Rafael R. Almeida6Niels O. S. Câmara7Momtchilo Russo8Institute of Biomedical Sciences, Department of Immunology, University of Sao Paulo, Sao Paulo 05508-000, BrazilInstitute of Biomedical Sciences, Department of Immunology, University of Sao Paulo, Sao Paulo 05508-000, BrazilInstitute of Biomedical Sciences, Department of Immunology, University of Sao Paulo, Sao Paulo 05508-000, BrazilInstitute of Biomedical Sciences, Department of Immunology, University of Sao Paulo, Sao Paulo 05508-000, BrazilInstitute of Biomedical Sciences, Department of Immunology, University of Sao Paulo, Sao Paulo 05508-000, BrazilInstitute of Molecular Medicine, University of Lisbon, 1649-028 Lisbon, PortugalInstitute of Biomedical Sciences, Department of Immunology, University of Sao Paulo, Sao Paulo 05508-000, BrazilInstitute of Biomedical Sciences, Department of Immunology, University of Sao Paulo, Sao Paulo 05508-000, BrazilInstitute of Biomedical Sciences, Department of Immunology, University of Sao Paulo, Sao Paulo 05508-000, BrazilElevated levels of immunoglobulin E (IgE) are associated with allergies and other immunological disorders. Sensitization with alum adjuvant favours IgE production while CpG-ODN adjuvant, a synthetic toll-like receptor 9 (TLR9) agonist, inhibits it. The cellular mechanisms underlying in vivo TLR regulation of immunoglobulin production, specially IgE, are still controversial. Specifically, TLR-mediated IgE regulation in vivo is not yet known. In this study we showed that augmented levels of IgE induced by sensitizations to OVA with or without alum adjuvant or with OVA-pulsed dendritic cells (DCs) were inhibited by co-administration of CpG. Notably, CpG-mediated suppression of IgE production required <i>MyD88</i>-expression on DCs but not on B-cells. This finding contrasts with previous in vitro studies reporting regulation of IgE by a direct action of CpG on B cells via MyD88 pathway. In addition, we showed that CpG also inhibited IgE production in a <i>MyD88</i>-dependent manner when sensitization was performed with OVA-pulsed DCs. Finally, CpG signalling through MyD88 pathway was also necessary and sufficient to prevent anaphylactic antibody production involved in active cutaneous anaphylaxis.https://www.mdpi.com/2073-4409/8/10/1165allergyigeigg2canaphylaxisdendritic cells |
spellingShingle | Ricardo W. Alberca Custodio Luciana Mirotti Eliane Gomes Fernanda P.B. Nunes Raquel S. Vieira Luís Graça Rafael R. Almeida Niels O. S. Câmara Momtchilo Russo Dendritic Cells Expressing MyD88 Molecule Are Necessary and Sufficient for CpG-Mediated Inhibition of IgE Production In Vivo Cells allergy ige igg2c anaphylaxis dendritic cells |
title | Dendritic Cells Expressing MyD88 Molecule Are Necessary and Sufficient for CpG-Mediated Inhibition of IgE Production In Vivo |
title_full | Dendritic Cells Expressing MyD88 Molecule Are Necessary and Sufficient for CpG-Mediated Inhibition of IgE Production In Vivo |
title_fullStr | Dendritic Cells Expressing MyD88 Molecule Are Necessary and Sufficient for CpG-Mediated Inhibition of IgE Production In Vivo |
title_full_unstemmed | Dendritic Cells Expressing MyD88 Molecule Are Necessary and Sufficient for CpG-Mediated Inhibition of IgE Production In Vivo |
title_short | Dendritic Cells Expressing MyD88 Molecule Are Necessary and Sufficient for CpG-Mediated Inhibition of IgE Production In Vivo |
title_sort | dendritic cells expressing myd88 molecule are necessary and sufficient for cpg mediated inhibition of ige production in vivo |
topic | allergy ige igg2c anaphylaxis dendritic cells |
url | https://www.mdpi.com/2073-4409/8/10/1165 |
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