Table 1.
Organ-specific determinants that can influence NK cell function*
| Organ-specific determinants | Liver | Mucosal tissues and skin | Uterus | Pancreas | Joints | Brain |
|---|---|---|---|---|---|---|
| Chemokines | Kupffer cell-derived CCL2, CXCL4, CXCL9, CXCL11, CXCL6 and CCL3 (Hs/Mm)16 | Lung: CCR2, CXCR3 and CX3CR1 ligands (Mm)16 | CXCL12 (Hs/Mm)74,75,76, 77,78,79,80,81,82 | CXCL10 (Mm)86 | CCR2 and CCR5 ligands (Hs)93,94 | Neuron-derived CX3CL1 and CX3CR1 expression on microglia (Mm)10 |
| Skin: TIG2, CXCR3 ligands and CCR5 ligands (Hs)65 | ||||||
| Unique cellular components | Kupffer cells, hepatic stellate cells, hepatocytes and NKT cells (Hs/Mm)42,52 | Gut: DCs adjacent to crytopatches; close proximity to epithelial stem cells and Paneth cells (Hs/Mm)67,68 | Invading trophoblasts; decidual stromal cells (Hs/Mm)71,72 | β-cells expressing RAE1 (an NKG2D ligand) and ligands for PD1 (Mm)85,88 | Osteoclasts, macrophages and monocytes (Hs/Mm)13,97 | Microglia, astrocytes and neuronal cells (Hs/Mm)1,106,107 |
| Skin: keratinocytes (Hs)63 | ||||||
| Soluble components | Abundance of IL-12 and IL-18; temporal IL-10 increase; frequent exposure to LPS (Hs/Mm)42,53,54,55 | Gut: IL-1 and IL-23 derived from DCs (Hs/Mm)68 | TGFβ derived from stromal cells (Hs)81; IL-15 (Hs/Mm)74; stem cell factor (Mm)17 | Effector T cell-derived cytokines and TReg cell-derived cytokines (Mm)6,85 | M-CSF, RANKL, IL-12, IL-15 and IL-18 (Hs/Mm)13,95,97,98,99 | Neurotransmitters; arrays of cytokines; proteins released by CNS-resident cells (Hs/Mm)1 |
| Lung: IL-15 from lung macrophages (Mm)64 | ||||||
| Skin: CCL5 and CXCL10 from keratinocytes (Hs)68 | ||||||
| Anatomical constituents | Exposure to food antigens and microbial products; perfusion with blood from the circulation and intestine; thin-walled sinusoids (Hs/Mm)28,42,43 | Gut: exposure to commensal microflora (Hs/Mm)68 | Mesometrial lymphoid aggregate of pregnancy (Hs/Mm)71 | β-cells in the islets of Langerhans (Hs/Mm)127 | Relative immune-privilege in normal conditions (Hs/Mm)13 | Distinctive blood–brain barrier in healthy conditions; neuro–immune–endocrine axis (Hs/Mm)2,100,128 |
| CCL, CC-chemokine ligand; CCR, CC-chemokine receptor; CNS, central nervous system; CX3CL, CX3C-chemokine ligand; CX3CR, CX3C-chemokine receptor; CXCL, CXC-chemokine ligand; CXCR, CXC-chemokine receptor; DC, dendritic cell; IL, interleukin; LPS, lipopolysaccharide; M-CSF, macrophage colony-stimulating factor; NK, natural killer; NKG2D, natural killer group 2, member D; NKT, natural killer T; PD1, programmed cell death protein 1; RAE1, retinoic acid early inducible 1; RANKL, receptor activator of NF-κB ligand; TGFβ, transforming growth factor-β; TIG2, tazarotene-induced gene 2 (also known as chemerin); TReg, regulatory T. | ||||||
| *'Hs' indicates evidence found in humans, 'Mm' indicates evidence found in mice, and 'Hs/Mm' indicates evidence found in both humans and mice. | ||||||