Impact of disease-modifying therapy on dendritic cells and exploring their immunotherapeutic potential in multiple sclerosis

Liu, Caiyun; Zhu, Jie; Mi, Yan; Jin, Tao

doi:10.1186/s12974-022-02663-z

Journal of Neuroinflammation

Table 2 Summary of strategies to induce autoantigen-specific tolDCs in vivo

From: Impact of disease-modifying therapy on dendritic cells and exploring their immunotherapeutic potential in multiple sclerosis

Receptors	Animal model	Coupled antigen	Targeting strategy	Mechanisms	Ref.
DEC205	MOG-induced EAE	MOG	Anti-DEC205	Prevent accumulation of effector T cells Promote enrichment of anti-MOG transgenic T cells Induce tolerance by tuning T cell responses through CD5 induction	[165]
			Single-chain fragment variables specific for DEC205	Induce a suppressive phenotype of DCs that expresses PD-L1 and secretes IL-10 and TGF-β Induce activated, IL-10-producing CD4⁺CD25⁺ FOXP3⁺ Tregs Reduce T_H1/T_H17 cells	[166]
			Anti-DEC205	Expand and induce antigen-specific FOXP3⁺ T cells	[167]
	PLP-induced EAE	PLP	Anti-DEC205	Reduce T_H17 cells Induce CD4⁺ FOXP3⁺ Tregs	[168]
MR	PLP-induced EAE	PLP	Mannosylation	Prevent CNS inflammation Induce a less-vigorous T_H1 response Induce antigen-specific tolerance	[174,175,176]
Langerin	MOG-induced EAE	MOG	Anti-langerin	Expand and induce antigen-specific FOXP3⁺ T cells	[167]
DC-SIGN	–	–	Coupling anti-DC-SIGN to porous silicon rapamycin-loaded nanoparticles	Promote the generation of Tregs	[191]
DCIR	MOG-induced EAE	MOG	Anti-DCIR2	Expand and induce antigen-specific FOXP3⁺ T cells	[167]
DCIR	PLP-induced EAE	PLP	Anti-DCIR2	Induce deletion and/or anergy in PLP-reactive T_H1/T_H17 cells Enhance the antigen-specific suppressor activity of FOXP3⁺ Tregs	[196]
DNGR-1	MOG-induced EAE	–	A fusion of anti-DNGR-1-IFNQ124R	Not shown	[203]
MICL	MOG/PLP-induced EAE	–	Anti-MICL or MICL knockout	Reduce DC infiltration within CNS^a	[206]
Siglec-H	MOG-induced EAE	MOG	Anti-Siglec-H	Inhibit CD4⁺ T cell expansion and T_H1/T_H17 cell polarization Fail to induce de novo generation of FOXP3⁺ Tregs	[211]
TLR9	MOG-induced EAE	–	Type A CpG ODNs	Reduce lymphocyte infiltration within CNS Induce tolerance phenotype of pDCs Inhibit T_H1/T_H17 immune response Induce expansion of Tregs and production of regulatory cytokines	[222]
	MOG/PLP-induced EAE	–	GpG ODNs	Reduce MHC-II expression Inhibit T_H1 immune response Promote T_H2 cell phenotype Reduce autoreactive B cell diversity	[223, 224]
	MOG-induced EAE	MOG	GpG-containing polyelectrolyte multilayers/polyplexes	Restrain TLR9 signaling and DC activation Inhibit T_H1/T_H17 immune response Induce CD4⁺CD25⁺ FOXP3⁺ Tregs	[226, 227]
MHC-II	MOG-induced EAE	MOG	Nanobodies recognizing MHC-II	Induce antigen-specific DC tolerance Elicit a burst of proliferation, followed by attrition, of MOG-specific CD4⁺ T cells	[228]

CD cluster of differentiation, CpG cytidine–phosphate–guanosine, DC dendritic cell, DCIR dendritic cell immunoreceptor, DC-SIGN dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin, DEC205 dendritic cell receptor for endocytosis-205, DNGR-1 dendritic cell natural killer lectin group receptor-1, EAE experimental autoimmune encephalomyelitis, IFN interferon, IL-10 interleukin-10, MHC major histocompatibility complex, MICL myeloid inhibitory C-type lectin receptor, MOG myelin oligodendrocyte glycoprotein, MR mannose receptor, ODNs oligodeoxynucleotides, pDCs plasmacytoid DCs, PD-L1 programmed cell death ligand 1, PLP proteolipid protein, Siglec-H Sialic-acid binding immunoglobulin-type lectin-H, TGF-β transforming growth factor-β, T_H T helper cells, TLR9 Toll-like receptor 9, Tregs regulatory T cells
^aThe MICL-mediated targeting DC-induced immune tolerance strategies remains in its infancy

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ISSN: 1742-2094

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