Dendritic cells and the extracellular matrix: A challenge for maintaining tolerance/homeostasis

Table 2 Dendritic cell interactions with extracellular matrix components

Class of component	ECM component	DC responses	DC receptors	Overall impact
Collagen	Soluble collagen I[74]	Murine BMDC upregulated CD86, IL-12, antigen uptake	DDR2	Pro-inflammatory
	Soluble collagen I[75]	Human MDDC increased IL-12p40, TNF-α, IFN-γ	DDR2	Pro-inflammatory
	Adsorbed collagen I, II, III[76]	Human MDDC increased maturation markers, pro-inflammatory cytokines, allostimulation	OSCAR	Pro-inflammatory
	Dermal hydrogel (laminin β3, collagen IV, VII)[77]	Decreased width of granulation tissue	-	Skin regeneration, anti-infl.
	Adsorbed fibronectin, collagen I, gelatin, Matrigel[78]	Murine myeloid DC on Matrigel were less mature (maturation marker, cytokines, morphology)	Adhesion complexes (CD29, CD49a-f, CD41, CD51, CD61)	Differential effects – Matrigel less inflammatory vs collagen I
	Collagen-like motifs in complement C1q[124]	Inhibits MDDC differentiation, TLR activity of pDC	LAIR-1	Anti-inflammatory
Glycoproteins	Pre-adsorbed laminin, fibronectin[79]	Human MDDC remained immature (maturation marker, high endocytosis)	Mannose receptor, DC-SIGN	Anti-inflammatory
	Modified Arg-Gly-Asp (RGD) on fibrillin[80]	Murine pDC adherence, TGB-β secretion increased in systemic sclerosis model	Integrins	Pro-fibrotic
Proteoglycans	Heparan sulfate[113,119]	DC maturation increased (morphology, costimulatory factors, T cell stimulation)	TLR4	Pro-inflammatory
		In GVHD blocking HS with alpha-1-antitrypsin limited alloreactive T cells	-	Pro-inflammatory
	Chondroitin sulfate[121]	Impact immunity in CNS pathologies	-	Pro- and anti-inflammatory
	DAMPs[111-113,117,118]	Activate DC	TLRs	Pro-infl.
Non-proteoglycan polysaccharides	Hyaluronan[82]	Increased hylauronan corresponds to decreased murine DC activation	-	Anti-inflammatory (tumours)
	Natural polymer hyaluronic acid[129,130]	Decreased DC maturation (maturation markers, cytokines, allostimulation)	-	Anti-inflammatory
Modulators	Secreted protein acidic and rich in cysteine[88]	Organization of germinal centres in LNs for TH17 by follicular DC	-	-
	Thrombospondin-1[89]	DC-derived thrombospondin inhibits resolution of inflammation	CD47, CD36	Anti-inflammatory
Enzymes	Matrix metalloproteinases[90]	Endogenous MMP-2 prime DC to TH2 (IL-12p70)	-	TH2 profile
	Tissue transglutaminases[151]	Influence DC activation (concentration-dependant)	-	Pro- and anti-inflammatory
Glycosylation modifications	Gut mucous[107]	Decrease in DC activation by inhibition of NF-κB	Dectin-1, galectin-3	Anti-inflammatory
	Tissue matrix in skin thymus, trachea[109]	Steady state homeostasis	MGL1+ MGL2+	Anti-inflammatory

DC: Dendritic cell; ECM: Extracellular matrix; OSCAR: Osteoclast-associated receptor; DDR: Discoidin domain receptors; IL: Interleukin-4; TNF-α: Tumour necrosis factor-α; IFN-γ: Interferon-γ; LAIR-1: Leukocyte-associated Ig-like receptor 1; TLR: Toll-like receptor; MGL: Macrophage galactose/N-acetylgalactosamine-specific C-type lectin.