Figure 4. Engineering tolerance in autoimmunity.

A) Untreated mice did not express high levels of scavenger receptor SRBII in the spleen. B) However, upon intravenous infusion of Ag-SP (PKH-76), SRBII was upregulated and some co-localization of SRBII and Ag-Sp was observed. C-D) Ag-SP co-localized with macrophages (F4/80), not DCs (CD11c), in the spleen.⁷⁵ E) Subcutaneous treatment of mice with antigen coupled QDs (MOG-QDs) resulted in drainage of QDs to the LN and co-localization with scavenger receptor MARCO expressing macrophages. F) Treating DCs with QDs coupled to varying doses of peptide did not elicit any inflammatory activation, measured by CD40 expression, in vitro. G) Treating EAE-induced mice with QDs coupled to a higher dose of peptide (52:1) resulted in a greater reduction in disease severity compared to mice treated with QDs coupled to a lower dose of peptide (17:1). Improvement was correlated with increased expansion of T_REGS in the LN.⁸⁰ H) Ag-ITE NPs increased expression of Socs2 in DCs in culture. I) Ag-ITE NPs inhibited translocation of Nf-ΚB into the nucleus. When treated with an inhibitor to Socs2 (siSocs2), translocation of Nf-ΚB into the nucleus was restored, indicating that Ag-ITE NP inhibited Nf-ΚB signaling via upregulation of Socs2.⁹¹ J-K) Intra-LN injection of Ag/Rapa-MPs resulted in reorganization of the LN while treatment with empty MPs did not cause any changes.¹⁰⁵ Panels adapted with permission from the indicated references.