@article {1327617,
	title = {Targeting DEC-205DCIR2 dendritic cells promotes immunological tolerance in proteolipid protein-induced experimental autoimmune encephalomyelitis},
	journal = {Mol Med},
	volume = {24},
	number = {1},
	year = {2018},
	month = {2018 May 03},
	pages = {17},
	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 CD11cCD8DEC-205 DCs.

METHODS: We employed a fusion between αDCIR2 antibodies and the highly encephalitogenic peptide 139-151 of myelin-derived proteolipid protein (PLP), to target CD11c CD8 DCs with a DEC-205-DCIR2 phenotype in vivo, and to substantially improve clinical symptoms in the PLP-induced model of experimental autoimmune encephalomyelitis (EAE).

RESULTS: Consistent with previous studies targeting other cell surface receptors, EAE protection mediated by αDCIR2-PLP fusion antibody (Ab) depended on an immature state of targeted DCIR2 DCs. The mechanism of αDCIR2-PLP 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 na{\"\i}ve CD4Foxp3 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.},
	issn = {1528-3658},
	doi = {10.1186/s10020-018-0017-6},
	author = {Tabansky, Inna and Keskin, Derin B and Watts, Deepika and Petzold, Cathleen and Funaro, Michael and Sands, Warren and Wright, Paul and Yunis, Edmond J and Najjar, Souhel and Diamond, Betty and Cao, Yonghao and Mooney, David and Kretschmer, Karsten and Stern, Joel N H}
}
