@article {1576532,
	title = {Steroid-Peptide Immunoconjugates for Attenuating T Cell Responses in an Experimental Autoimmune Encephalomyelitis Murine Model of Multiple Sclerosis},
	journal = {Bioconjug Chem},
	volume = {31},
	number = {12},
	year = {2020},
	month = {2020 12 16},
	pages = {2779-2788},
	abstract = {Diseases of immunity, including autoimmune diseases such as multiple sclerosis, transplantation graft rejection, allergy, and asthma, are prevalent and increasing in prevalence. They contribute to significant morbidity and mortality; however, few if any curative therapies exist, and those that are available lack either potency or specificity. Dendritic cells (DCs) are sentinels of the immune system that connect the innate and adaptive immune system and are critical regulators of both immunity and tolerance. We posited that the tolerogenic potential of DC could be harnessed to develop more specific and potent therapies for diseases of immunity by delivering autoantigen to a sufficient number of tolerogenic DCs in situ that could then inhibit pathogenic effector T cell responses. Specifically, we hypothesized that the steroid dexamethasone covalently coupled to a peptide antigen could be processed by DCs, induce tolerogenic DCs, and attenuate antigen-specific pathogenic T cell responses. To test this hypothesis, we synthesized a series of dexamethasone-peptide immunoconjugates by standard solid-phase peptide synthesis. The antigenic portion of the immunoconjugate could be presented by DCs, and the immunoconjugate induced a tolerogenic phenotype in DCs that then inhibited antigen-specific T cell proliferation in vitro. When the immunoconjugate was administered prophylactically in the murine experimental autoimmune encephalomyelitis model of multiple sclerosis, disease was attenuated compared to dexamethasone and peptide delivered as uncoupled components. Together, this work demonstrates the utility of immunoconjugates for inducing tolerance while establishing the foundation for future studies exploring methods to enrich and target DCs for tolerogenic therapies.},
	keywords = {Adaptive Immunity, Animals, Dexamethasone, Encephalomyelitis, Autoimmune, Experimental, Immunity, Innate, Immunoconjugates, Mice, Multiple Sclerosis, Peptides, T-Lymphocytes},
	issn = {1520-4812},
	doi = {10.1021/acs.bioconjchem.0c00582},
	author = {Sands, R Warren and Tabansky, Inna and Verbeke, Catia S and Keskin, Derin and Michel, Samuel and Stern, Joel and Mooney, David J}
}
