title: Boosting Adaptive Immunity: A New Role for PAFR Antagonists.
abstract: We have previously shown that the Platelet-Activating Factor Receptor (PAFR) engagement in murine macrophages and dendritic cells (DCs) promotes a tolerogenic phenotype reversed by PAFR-antagonists treatment in vitro. Here, we investigated whether a PAFR antagonist would modulate the immune response in vivo. Mice were subcutaneously injected with OVA or OVA with PAFR-antagonist WEB2170 on days 0 and 7. On day 14, OVA-specific IgG2a and IgG1 were measured in the serum. The presence of WEB2170 during immunization significantly increased IgG2a without affecting IgG1 levels. When WEB2170 was added to OVA in complete Freund's adjuvant, enhanced IgG2a but not IgG1 production was also observed, and CD4+ FoxP3+ T cell frequency in the spleen was reduced compared to mice immunized without the antagonist. Similar results were observed in PAFR-deficient mice, along with increased Tbet mRNA expression in the spleen. Additionally, bone marrow-derived DCs loaded with OVA were transferred into naïve mice and their splenocytes were co-cultured with fresh OVA-loaded DCs. CD4+T cell proliferation was higher in the group transferred with DCs treated with the PAFR-antagonist. We propose that the activation of PAFR by ligands present in the site of immunization is able to fine-tune the adaptive immune response.
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Marianna M
authors.initials: MM
authors.lastname: Koga
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Bruna
authors.initials: B
authors.lastname: Bizzarro
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Anderson
authors.initials: A
authors.lastname: Sá-Nunes
authors.affiliation: Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Rios
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Sonia
authors.initials: S
authors.lastname: Jancar
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001381:Azepines / Q000008:administration & dosage* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D005620:Freund's Adjuvant / Q000008:administration & dosage / Q000276:immunology; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood*; D051379:Mice; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000276:immunology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D014230:Triazoles / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D001381:Azepines; D007074:Immunoglobulin G; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; C039351:platelet activating factor receptor; D010047:Ovalbumin; D005620:Freund's Adjuvant; C063964:bepafant