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

Table 1 Dendritic cells and the maintenance of homeostasis in different tissues

Tissue	Location	Resident DC in naïve tissue	Resident associated cells/naïve tissue	Stromal/cellular interactions in immune homeostasis	Ref.
Skin	Epidermis	Cd1a+ Langerin+ Langerhans cells expressing Birbeck granules	Keratinocytes	E-cadherin junctions with keratinocytes, TGF-β production, tolerogenic Treg responses	[6, 40-42]
	Dermis	CD1c+ DC-SIGN+ DEC205+ dermal DC subsets (Langerin+ CD11blow, Langerin-CD11b-, and Langerin-CD11blow)	To be elucidated (presumed dermal matrix, fibroblasts)	Pluripotent dermal DC may present antigen, migrate or reside in tissue depending on local interactions	[69, 144]
Intestinal mucosa	LP, Peyer’s patches, GALT, SILT	CD103+CD11b+ or CD103+ CD11b-migratory DC, CD103+Sirpα- DC, pDC, CX3CR1+ DC	Macrophages, B cells	Maintain immune homeostasis, induce Treg differentiation, oral tolerance (TGF-β, Treg, TH2 factors)	[5, 48-50, 145, 146]
				Gut: Retinoic acid, TH17 cells
				LP: indoleamine 2,3-dioxygenase
				CD83 on DC regulates mucosal tolerance
Liver	Portal tracts, interstitial DC	CD103+DC, CD103-DC, CD103-CD11b+DC, CD141+ DC (high in healthy liver)	Hepatic stellate cells, sinusoidal endothelial cells, Kupffer cells, hepatocytes	Inhibit DC activation (indoleamine-2,3-dioxygenase expression), repress T cell activation (IL-10, TGF-β) via CTLA-4, PD-1	[4, 51, 52,147,148]
Cornea	Central/peripheral corneal stroma	CD11b+ CD11c+ DC, B220+ CD11clo pDC, CD34+ MHCII myeloid precursors	Stromal Collagen I, CD11b+ CD11c- macrophages, keratocytes	Maintain MHCIIlow CD80low CD86low phenotype under normal conditions	[54-57]
Spleen	Marginal zones	Lymphoid, myeloid and pDC	Macrophages, T cells, B cells (zone dependant)	To be elucidated	[58-60]
Bone marrow	Osteoblastic or vascular niches	Resident hematopoietic stem cell DC progenitors	Osteoblasts, stromal cells and sinusoidal endothelial cells	-	[61]
Retina	Peripheral margins and juxtapapillary areas	Presence of DCs is debated.	Likely migrated in from choroid, ciliary body and meninges	Perivasulcar - around retinal venules (initial site of immune disruption), but not arterioles.	[149]
		Few MHCII+ 33D1+ DC observed in naïve brain
Brain	Regions of synaptic plasticity and neurogenesis	Presence of DCs is debated.	-	-	[62,63,150]
		Brain-derived CD11c+ DC
Bone/cartilage/vitreous	Not detected	-	-	-	-

DC: Dendritic cell; TGF-β: Transforming growth factor-β; LP: Lamina propria; GALT: Gut-associated lymphoid tissues; SILT: Solitary intestinal lymphoid tissue; MHCII: Major histocompatibility complex class II; IL: Interleukin-4.