PMID- 31569343 OWN - NLM STAT- MEDLINE DCOM- 20200615 LR - 20200615 IS - 2073-4409 (Electronic) IS - 2073-4409 (Linking) VI - 8 IP - 10 DP - 2019 Sep 28 TI - Dendritic Cells Expressing MyD88 Molecule Are Necessary and Sufficient for CpG-Mediated Inhibition of IgE Production In Vivo. LID - 10.3390/cells8101165 [doi] LID - 1165 AB - 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 MyD88-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 MyD88-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. FAU - Alberca Custodio, Ricardo W AU - Alberca Custodio RW AUID- ORCID: 0000-0002-3602-3306 AD - Institute of Biomedical Sciences, Department of Immunology, University of Sao Paulo, Sao Paulo 05508-000, Brazil. Ricardowesley@gmail.com. FAU - Mirotti, Luciana AU - Mirotti L AD - Institute of Biomedical Sciences, Department of Immunology, University of Sao Paulo, Sao Paulo 05508-000, Brazil. lmirotti@gmail.com. FAU - Gomes, Eliane AU - Gomes E AD - Institute of Biomedical Sciences, Department of Immunology, University of Sao Paulo, Sao Paulo 05508-000, Brazil. melloeag@gmail.com. FAU - Nunes, Fernanda P B AU - Nunes FPB AD - Institute of Biomedical Sciences, Department of Immunology, University of Sao Paulo, Sao Paulo 05508-000, Brazil. FAU - S Vieira, Raquel AU - S Vieira R AD - Institute of Biomedical Sciences, Department of Immunology, University of Sao Paulo, Sao Paulo 05508-000, Brazil. raqueldesouzavieira@outlook.com. FAU - Graca, Luis AU - Graca L AD - Institute of Molecular Medicine, University of Lisbon, 1649-028 Lisbon, Portugal. lgraca@medicina.ulisboa.pt. FAU - R Almeida, Rafael AU - R Almeida R AD - Institute of Biomedical Sciences, Department of Immunology, University of Sao Paulo, Sao Paulo 05508-000, Brazil. rafaelbio13@yahoo.com.br. FAU - S Camara, Niels O AU - S Camara NO AD - Institute of Biomedical Sciences, Department of Immunology, University of Sao Paulo, Sao Paulo 05508-000, Brazil. niels@icb.usp.br. FAU - Russo, Momtchilo AU - Russo M AD - Institute of Biomedical Sciences, Department of Immunology, University of Sao Paulo, Sao Paulo 05508-000, Brazil. momrusso@usp.br. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190928 PL - Switzerland TA - Cells JT - Cells JID - 101600052 RN - 0 (Adjuvants, Immunologic) RN - 0 (CPG-oligonucleotide) RN - 0 (Myd88 protein, mouse) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (Oligodeoxyribonucleotides) RN - 37341-29-0 (Immunoglobulin E) RN - 9006-59-1 (Ovalbumin) SB - IM MH - Adjuvants, Immunologic/*administration & dosage/pharmacology MH - Animals MH - B-Lymphocytes/drug effects/immunology/metabolism MH - Dendritic Cells/drug effects/*immunology/metabolism MH - Disease Models, Animal MH - Female MH - Gene Expression Regulation/drug effects MH - Humans MH - Immunoglobulin E/drug effects/*metabolism MH - Mice MH - Myeloid Differentiation Factor 88/genetics/*metabolism MH - Oligodeoxyribonucleotides/*administration & dosage/pharmacology MH - Ovalbumin/*adverse effects MH - Respiratory Hypersensitivity/chemically induced/*drug therapy/metabolism MH - Signal Transduction/drug effects PMC - PMC6829343 OTO - NOTNLM OT - IgE OT - IgG2c OT - allergy OT - anaphylaxis OT - dendritic cells COIS- The authors declare no conflict of interest. EDAT- 2019/10/02 06:00 MHDA- 2020/06/17 06:00 PMCR- 2019/10/01 CRDT- 2019/10/02 06:00 PHST- 2019/08/09 00:00 [received] PHST- 2019/09/23 00:00 [revised] PHST- 2019/09/25 00:00 [accepted] PHST- 2019/10/02 06:00 [entrez] PHST- 2019/10/02 06:00 [pubmed] PHST- 2020/06/17 06:00 [medline] PHST- 2019/10/01 00:00 [pmc-release] AID - cells8101165 [pii] AID - cells-08-01165 [pii] AID - 10.3390/cells8101165 [doi] PST - epublish SO - Cells. 2019 Sep 28;8(10):1165. doi: 10.3390/cells8101165.