Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Dendritic Cells Expressing MyD88 Molecule Are Necessary and Sufficient for CpG-Mediated Inhibition of IgE Production in Vivo

Ricardo Wesley Alberca-Custódio
ORCID logo ,
Luciana Mirotti
,
Eliane Gomes
,
Fernanda Peixoto Barbosa Nunes
,
Raquel Souza Vieira
,
Luis Graça
,
Rafael Ribeiro Almeida
,
Niels Olsen Saraiva Câmara
,
Momtchilo Russo
*
Version 1 : Received: 9 August 2019 / Approved: 11 August 2019 / Online: 11 August 2019 (07:32:32 CEST)

A peer-reviewed article of this Preprint also exists.

Alberca Custodio, R.W.; Mirotti, L.; Gomes, E.; Nunes, F.P.; S. Vieira, R.; Graça, L.; R. Almeida, R.; S. Câmara, N.O.; Russo, M. Dendritic Cells Expressing MyD88 Molecule Are Necessary and Sufficient for CpG-Mediated Inhibition of IgE Production In Vivo. Cells 2019, 8, 1165. Alberca Custodio, R.W.; Mirotti, L.; Gomes, E.; Nunes, F.P.; S. Vieira, R.; Graça, L.; R. Almeida, R.; S. Câmara, N.O.; Russo, M. Dendritic Cells Expressing MyD88 Molecule Are Necessary and Sufficient for CpG-Mediated Inhibition of IgE Production In Vivo. Cells 2019, 8, 1165.

Abstract

Elevated levels of immunoglobulin E (IgE) are associated with allergies and other immunological disorders. Experimentally, sensitization with alum adjuvant favors IgE production while CpG-ODN adjuvant, a synthetic toll-like receptor 9 (TLR9) agonist, inhibits it. The cellular mechanisms underlying TLR-regulation of immunoglobulin production are still controversial. Specifically, TLR-mediated IgE regulation in vivo is not yet known. We show that augmented levels of IgE induced by sensitizations to OVA with or without alum adjuvant or with OVA-pulsed dendritic cells (DCs) were inhibited when sensitization to OVA was performed in the presence of CpG. Notably, CpG-mediated suppression of IgE production required MyD88-expression on DCs but not on B-cells. This contrasts with previous reports of in vitro regulation IgE where CpG acted directly on B cells via MyD88 pathway. In addition, CpG also inhibited IgE production in a MyD88-dependent manner when sensitization was performed with OVA-pulsed DCs. Finally, CpG signaling through MyD88 pathway was also necessary and sufficient to prevent anaphylactic antibody production involved in active cutaneous anaphylaxis.

Keywords

allergy; IgE; IgG2c; anaphylaxis; dendritic cells

Subject

Medicine and Pharmacology, Immunology and Allergy

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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