{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Tabansky I"],"funding":["National Institutes of Health"],"pagination":["17"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6016871"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["24(1)"],"pubmed_abstract":["BACKGROUND:Dendritic cells (DC) induce adaptive responses against foreign antigens, and play an essential role in maintaining peripheral tolerance to self-antigens. Therefore they are involved in preventing fatal autoimmunity. Selective delivery of antigens to immature DC via the endocytic DEC-205 receptor on their surface promotes antigen-specific T cell tolerance, both by recessive and dominant mechanisms. We provide evidence that the induction of antigen-specific T cell tolerance is not a unique property of CD11c+CD8+DEC-205+ DCs. METHODS:We employed a fusion between αDCIR2 antibodies and the highly encephalitogenic peptide 139-151 of myelin-derived proteolipid protein (PLP139-151), to target CD11c +CD8- DCs with a DEC-205-DCIR2+ phenotype in vivo, and to substantially improve clinical symptoms in the PLP139-151-induced model of experimental autoimmune encephalomyelitis (EAE). RESULTS:Consistent with previous studies targeting other cell surface receptors, EAE protection mediated by αDCIR2-PLP139-151 fusion antibody (Ab) depended on an immature state of targeted DCIR2+ DCs. The mechanism of αDCIR2-PLP139-151 mAb function included the deletion of IL-17- and IFN-γ-producing pathogenic T cells, as well as the enhancement of regulatory T (Treg) cell activity. In contrast to the effect of αDEC-205+ fusion antibodies, which involves extrathymic induction of a Foxp3+ Treg cell phenotype in naïve CD4+Foxp3- T cells, treatment of animals with DCIR2+ fusion antibodies resulted in antigen-specific activation and proliferative expansion of natural Foxp3+ Treg cells. CONCLUSIONS:These results suggest that multiple mechanisms can lead to the expansion of the Treg population, depending on the DC subset and receptor targeted."],"journal":["Molecular medicine (Cambridge, Mass.)"],"pubmed_title":["Targeting DEC-205-DCIR2+ dendritic cells promotes immunological tolerance in proteolipid protein-induced experimental autoimmune encephalomyelitis."],"pmcid":["PMC6016871"],"funding_grant_id":["NICHD F32 081835."],"pubmed_authors":["Funaro M","Wright P","Diamond B","Petzold C","Keskin DB","Najjar S","Mooney D","Sands W","Watts D","Kretschmer K","Cao Y","Stern JNH","Tabansky I","Yunis EJ"],"additional_accession":[]},"is_claimable":false,"name":"Targeting DEC-205-DCIR2+ dendritic cells promotes immunological tolerance in proteolipid protein-induced experimental autoimmune encephalomyelitis.","description":"BACKGROUND:Dendritic cells (DC) induce adaptive responses against foreign antigens, and play an essential role in maintaining peripheral tolerance to self-antigens. Therefore they are involved in preventing fatal autoimmunity. Selective delivery of antigens to immature DC via the endocytic DEC-205 receptor on their surface promotes antigen-specific T cell tolerance, both by recessive and dominant mechanisms. We provide evidence that the induction of antigen-specific T cell tolerance is not a unique property of CD11c+CD8+DEC-205+ DCs. METHODS:We employed a fusion between αDCIR2 antibodies and the highly encephalitogenic peptide 139-151 of myelin-derived proteolipid protein (PLP139-151), to target CD11c +CD8- DCs with a DEC-205-DCIR2+ phenotype in vivo, and to substantially improve clinical symptoms in the PLP139-151-induced model of experimental autoimmune encephalomyelitis (EAE). RESULTS:Consistent with previous studies targeting other cell surface receptors, EAE protection mediated by αDCIR2-PLP139-151 fusion antibody (Ab) depended on an immature state of targeted DCIR2+ DCs. The mechanism of αDCIR2-PLP139-151 mAb function included the deletion of IL-17- and IFN-γ-producing pathogenic T cells, as well as the enhancement of regulatory T (Treg) cell activity. In contrast to the effect of αDEC-205+ fusion antibodies, which involves extrathymic induction of a Foxp3+ Treg cell phenotype in naïve CD4+Foxp3- T cells, treatment of animals with DCIR2+ fusion antibodies resulted in antigen-specific activation and proliferative expansion of natural Foxp3+ Treg cells. CONCLUSIONS:These results suggest that multiple mechanisms can lead to the expansion of the Treg population, depending on the DC subset and receptor targeted.","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 May","modification":"2025-04-04T19:33:57.526Z","creation":"2019-03-26T23:52:11Z"},"accession":"S-EPMC6016871","cross_references":{"pubmed":["30134798"],"doi":["10.1186/s10020-018-0017-6"]}}