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Targeting DEC-205-DCIR2+ dendritic cells promotes immunological tolerance in proteolipid protein-induced experimental autoimmune encephalomyelitis.

ABSTRACT: 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.We employed a fusion between ?DCIR2 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).Consistent with previous studies targeting other cell surface receptors, EAE protection mediated by ?DCIR2-PLP139-151 fusion antibody (Ab) depended on an immature state of targeted DCIR2+ DCs. The mechanism of ?DCIR2-PLP139-151 mAb function included the deletion of IL-17- and IFN-?-producing pathogenic T cells, as well as the enhancement of regulatory T (Treg) cell activity. In contrast to the effect of ?DEC-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.These results suggest that multiple mechanisms can lead to the expansion of the Treg population, depending on the DC subset and receptor targeted.

SUBMITTER: Tabansky I

PROVIDER: S-EPMC6016871 | biostudies-other | 2018 May

REPOSITORIES: biostudies-other

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Targeting DEC-205<sup>-</sup>DCIR2<sup>+</sup> dendritic cells promotes immunological tolerance in proteolipid protein-induced experimental autoimmune encephalomyelitis.

Tabansky Inna I Keskin Derin B DB Watts Deepika D Petzold Cathleen C Funaro Michael M Sands Warren W Wright Paul P Yunis Edmond J EJ Najjar Souhel S Diamond Betty B Cao Yonghao Y Mooney David D Kretschmer Karsten K Stern Joel N H JNH

Molecular medicine (Cambridge, Mass.) 20180503 1

<h4>Background</h4>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 n ...[more]

PMID: 30134798

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Dataset Information

Targeting DEC-205-DCIR2+ dendritic cells promotes immunological tolerance in proteolipid protein-induced experimental autoimmune encephalomyelitis.

Publications

Targeting DEC-205<sup>-</sup>DCIR2<sup>+</sup> dendritic cells promotes immunological tolerance in proteolipid protein-induced experimental autoimmune encephalomyelitis.

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