. Author manuscript; available in PMC: 2013 Apr 9.

Published in final edited form as: Nat Rev Immunol. 2011 Sep 23;11(10):658–671. doi: 10.1038/nri3065

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)^74–82	CXCL10 (Mm)⁸⁶	CCR2 and CCR5 ligands (Hs)^93,94	Neuron-derived CX₃CL1 and CX₃CR1 expression on microglia (Mm)¹⁰
Chemokines		Skin: TIG2, CXCR3 ligands and CCR5 ligands (Hs)⁶⁵	CXCL12 (Hs/Mm)^74–82	CXCL10 (Mm)⁸⁶	CCR2 and CCR5 ligands (Hs)^93,94
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)^1,106,109
Unique cellular components		Skin: keratinocytes (Hs)⁶³	Invading trophoblasts; decidual stromal cells (Hs/Mm)^71,72		Osteoclasts, macrophages and monocytes (Hs/Mm)^13,97	Microglia, astrocytes and neuronal cells (Hs/Mm)^1,106,109
Soluble components	Abundance of IL-12 and IL-18; temporal IL-10 increase; frequent exposure to LPS (Hs/Mm)^42,53–55	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 T_Reg cell-derived cytokines (Mm)^6,85	M-CSF, RANKL, IL-12, IL-15 and IL-18 (Hs/Mm)^{13,95,97–99}	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); T_Reg, 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.