TABLE 1.
Summary of approaches to inducing tolDC in vivo.
| Experimental mode | Tolerizing approach | Cells targeted | Specificity | Timing | Results | References |
| EAE (PLP, SJL) | PLP Ag delivery | cDC1 + LC | DEC205 Ab | −10 d/−15 d | Prevent and reduce disease severity ∼prevent Ag response + T suppressive mechanism | [72] |
| EAE (MOG, C57Bl/6) | MOG Ag delivery | pDC | SiglecH Ab | −1 d | Delay onset and reduce disease ∼prevent Ag response, no effect Tregs | [73] |
| EAE (MOG, C57Bl/6) | NP + peptide + AhR ligand | APC | Non-specific | d0 | Suppress disease progression ∼expand Tregs | [79] |
| EAE (MOG, C57Bl/6) | MOG Ag delivery | cDC1 + LC cDC1 migratory cDC1 resident cDC2 | DEC205 Ab Langerin Ab Treml4 Ab DCIR2 Ab | −14 d −14 d −14 d −14 d | Prevent and reduce disease Prevent and reduce disease Prevention/reduction minimal Prevention/reduction minimal ∼Protection correlates with Treg generation | [71] |
| EAE (spinal cord, C57Bl/6) | MOG Ag delivery | cDC1 + LC | DEC205 scFv | −7 and −3 d or +7 and 11 d | Prevent disease TGFβ-dependently ∼reduce IL-17 & IFNγ in CD4+ T cells ∼induce TGFβ+ capacity in DCs | [19] |
| EAE (MOG, C57Bl/6) | NP + peptide + IL-10 | APC | Non-specific | −30 and −15d or +8 and 22d | Reduce disease severity ∼reduced IFNγ and IL-17 by splenic T cells | [77] |
| EAE (PLP, SJL) | Highly negative MP | Inflammatory mono | via MARCO | +7 d; start relapse | Prevent disease; relapse ∼reduced inflammation CNS (especially DC) | [81] |
| EAE (MOG, C57Bl/6; MPB, B10.PL) | NP + Ag | Liver sinus EC accumulation | Selected NP | +1 d; +8−12 d | Prevent; reduce disease score ∼TGFβ and Treg dependently | [90] |
| EAE (PLP, SJL) | NP + Ag + rapamycin | APC | Non-specific | −14 and −21 d; +13 d | Prevent disease; relapse ∼prevent Ag response, induce Treg/Breg | [78] |
| EAE (MOG, PLP, C57Bl/6) | NP + MHCII-MOG-peptide or MHCII-PLP-peptide | APC | Non-specific | +14 d; +21 d | Reduce disease severity ∼Ag-ex perienced Teff→Tr1 (APC-dependent) ∼formation and expansion Bregs | [80] |
| EAE (MOG, C57Bl/6) | MOG Ag decorated rbc | Phagocytes | Non-specific | 7 d/+5 d/+11 d | Prevent or cure disease ∼Th17 decrease in CNS | [83] |
| EAE (PLP, SJL) | NP + peptide + rapamycin | APC | Non-specific | +14 d = peak | Prevent relapse ∼prevent Ag response + expand Tregs | [74] |
| EAE (PLP, SJL) | PLP Ag delivery | CD11b+ cDC2 | DCIR2 Ab | −10d | Prevent and reduce disease ∼reduce pathogenic TH + expand Tregs | [20] |
| EAE (MOG, C57Bl/6) | Engineered IFNα delivery | pDC, cDC1 | SiglecH sdAb or Clec9A sdAb | +7 d/+12 d | Delay onset, reduce disease progression ∼IDO/TGFβ+ pDC; IL-10/TGFβ+ Treg and Bregs | [89] |
| Diabetes (p31-T transfer) | p31 peptide delivery | rbc → uptake DC | Ly76 scFv → non-specific | +8 h till 7 d | Prevent hyperglycemia ∼deletion transferred diabetogenic T cells | [91] |
| Diabetes (NOD/BDC2.5) | NP + IAg7 (NOD/BDC2.5 MHCII) | APC | Non-specific | 10 wk of age | Prevent incidence ∼Ag-experienced Teff → Tr1 (APC-dependent) ∼formation and expansion Bregs | [80] |
| Diabetes (NOD+BDC2.5-T) | BDC2.5 peptide delivery | cDC2 cDC1 | DCIR2 Ab DEC205 Ab | −1 and 0 d −1 and 0 d | Delay diabetes induction ∼ T cell apoptosis no effect | [24] |
| Diabetes (NOD mice) | NP + Ins Ag + AhR ligand | APC | Non-specific | 8 wk of age | Reduce disease development ∼tolDC, Treg differentiation | [92] |
| Diabetes (NOD mice) | Ins Ag decorated rbc | Phagocytes | Non-specific | 10 wk of age | 80% protection | [83] |
| IBD (DSS, C57Bl/6) | Highly negative MP | Inflammatory mono | via MARCO | +1−6 d | Suppress disease score ∼reduced inflammation/colon | [81] |
| Inflammatory arthritis | liposomes + Ag + NFκB⊥ | cDC, pDC, mf | Non-specific | +6 d | Reduce disease severity ∼induction Tregs, suppression Teffs | [76] |
| Arthritis (CIA) | NP + MHCII-collagen peptide | APC | Non-specific | @130% swelling | Reduce disease severity ∼Ag-experienced Teff → Tr1 (APC-dependent) ∼formation and expansion Bregs | [80] |
| Skin transplantation | MHC-I monomer delivery | cDC2 | DCIR2 Ab | −14 d | Long term allograft survival if CD8-depleted | [93] |
| Liver transplantation | NP + tacrolimus | APC | Non-specific | +4 till 10 d | Prolong allograft survival | [94] |
| Heart transplantation | Targeted NP + αCD3 | HEV, LN | MECA79 Ab | −1 d till 3 d | Prolong allograft survival ∼Treg dependent | [95] |
| Heart transplantation | HDL-NP + rapamycin | Myeloid cells (mf) | Non-specific | +6 d | Long term allograft survival ∼Mreg dependent | [96] |
Ab, antibody; Ag, antigen; AhR, Aryl hydrocarbon receptor; APC, antigen-presenting cell; cDC, conventional dendritic cell; d, day; EC, endothelial cell; HEV, high endothelial venules; Ins, insulin; LC, Langerhans cell; LN, lymph node; mf, macrophages; MOG, myelin oligodendrocyte glycoprotein; mono, monocytes; MP, microparticles; NP, nanoparticles; pDC, plasmacytoid dendritic cell; PLP, proteolipid protein; rbc, red blood cells; sdAb, single-domain antibody; scFv, single-chain variable fragment; wk, week.