Table 2.
Unique features of NK cells in distinct organs*
| Cell features and functions | Liver | Mucosal tissues and skin | Uterus | Pancreas | Joints | Brain |
|---|---|---|---|---|---|---|
| Receptor expression | NKG2A ↑, LY49 ↑, CD56low and CD16 ↓ (Hs/Mm)44,49,50 | Gut: RORγt+LIN−, RORγt+NKp46+NK1.1int, CD127+NKp46low, CD122intc-Kit+ and KIR− (Hs)65,67–69; LY49− (Mm)68 | CD16−CD56hi (Hs)75; NKp46+ (Hs/Mm)75; CD3−CD122+, LY49+, NK1.1− and DX5− (Mm)76,79 | KLRG1 ↑; NK cells from NOD mice express more NKC gene products than NK cells from B6.H-2g7 mice; CD25 and CD69 (Mm)6,85 | CD56hiCD16− ↑, CD94–NKG2A ↑ (Hs)87,92,95,96; RANKL+, chemokine receptors ↑ (Hs/Mm)13,99; M-CSFR+, adhesion molecules ↑ (Mm)13,97,98 | NKG2A ↑ (Mm)11,12; nicotinic acetylcholine receptors ↑ (Mm)‡ |
| Lung: LY49hi (Mm)64,66 | ||||||
| Skin: CD56hiCD16−CD158b−(Hs)63 | ||||||
| Effector molecule expression | NKp44+, NKG2C+, TRAIL ↑, perforin and granzymes ↑ (Mm)44,49,50 | Gut: IL-22+, IL-17+, IFNγ− and perforin ↓ (Hs/Mm)67 | CXCL8 and CXCL12 ↑ (Hs)82; IFNγ, VEGF and PLGF ↑ (Mm)74,78 | PD1+ and LAMP1+ (Mm)85,88 | Granzymes and IFNγ (Hs/Mm)13,87,92 | IFNγ, perforin and granzymes ↑ (Mm)11,12 |
| Lung: factors that enhance macrophage function (Mm)64 | ||||||
| Skin: IFNγ (Hs)63 | ||||||
| Cytotoxicity and proliferation | Increased early, decreased at later stages (Hs/Mm)42 | Gut: reduced or absent (Hs/Mm)67,68 | ADCC and cytotoxicity decreased (Hs)81 | Proliferation and degranulation increased early and decreased at later stages (Mm)85 | Increased (Mm)13 | Increased cytotoxicity against microglia (Mm)11,12 |
| Other functions | Crosstalk with Kupffer and NKT cells (Hs/Mm)42; promote TReg cells (Mm)51 | Control inflammation (Hs/Mm)67,84 | Regulate endometrial remodelling, angiogenesis and implantation (Hs/Mm)71; uterine NK cell-derived IFNγ modifies vascularity (Mm)78 | Reciprocal interactions with effector and TReg cells (Mm)6 | Promote formation of osteoclasts; colocalize with monocytes and promote their TNF production (Mm)13 | Condition the CNS; release cytokines; suppress myelin-specific TH17 cells (Mm)11,12 |
| Gut: TH17 cell-like functions; respond to DC-derived IL-23 and IL-1, but not IL-15; sustain lymphoid tissue integrity; promote tissue repair (Hs/Mm)67,68 | ||||||
| ADCC, antibody-dependent cell-mediated cytotoxicity; CNS, central nervous system; CXCL, CXC-chemokine ligand; DC, dendritic cell; IFNγ, interferon-γ; IL, interleukin; KLRG1, killer cell lectin-like receptor subfamily G member 1; LAMP1, lysosomal-associated membrane protein; LIN−, lineage negative; M-CSF, macrophage colony-stimulating factor; NK, natural killer; NKC, natural killer gene complex; NKG2, natural killer group 2; NKT, natural killer T; NOD, non-obese diabetic; PLGF, placental growth factor; RANKL, receptor activator of NF-κB ligand; TH17, T helper 17; TNF, tumour necrosis factor; TRAIL, TNF-related apoptosis-inducing ligand; TReg, regulatory T; VEGF, vascular endothelial growth factor. | ||||||
| *'Hs' indicates evidence found in humans, 'Mm' indicates evidence found in mice, and 'Hs/Mm' indicates evidence found in both humans and mice. | ||||||
| ‡Unpublished observations (F.-D.S.). | ||||||