Table 1.
NHR Classification, distribution and function in immune cells.a)
| Official Name | Gene Symbolb | Common Name | Ligands | Expressionc | Function |
|---|---|---|---|---|---|
| NR1A1 | THRA | Thyroid hormone receptor α | Thyroid hormones | preT, ILC3, S | T/B dev [97] |
| NR1A2 | THRB | Thyroid hormone receptor β | Thyroid hormones | DC,M,S | ND |
| NR1B1 | RARA | Retinoic acid receptor α | Retinoic acid (RA) | M, Ne | Reg B, DC, T, Lti [48, 98] |
| NR1B2 | RARB | Retinoic acid receptor β | RA | DC, M | Reg B, DC, T, Lti [48, 98] |
| NR1B3 | RARG | Retinoic acid receptor γ | RA | γδT cells | Reg B, DC, T, Lti [48, 98] |
| NR1C1 | PPARA | Pparα | Fatty acids, phospholipid [99] | no signal | DC, M diff and function [100] |
| NR1C2 | PPARD | Pparδ | Fatty acids | ILCs, Ne, S | ND |
| NR1C3 | PPARG | Pparγ | Fatty acids, PGJ2 | αβT, ILC2, M, S | ND |
| NR1D1 | NR1D1 | Rev-erbα | Heme [101] | ILC2/3, γδT, S | TLR IECs [58] |
| NR1D2 | NR1D2 | Rev-erbβ | Heme [101] | uncertain | ND |
| NR1F1 | RORA | RAR-related orphan receptor α | CBIs [42], cholesterol, CS | αβT, ILCs | TLR IECs [58], T cells dev. |
| NR1F2 | RORB | RAR-related orphan receptor β | retinoic acid | no signal | ND |
| NR1F3 | RORC | RAR-related orphan receptor γ | CBIs, oxysterols [42, 67] | αβT, γδT, ILC3 | Lymphoid, Th17[55, 56, 93] |
| NR1H3 | LXRA | Liver X receptor α | CBIs [68, 70] oxysterols | M,,S | M [68], T,B, prolfieration [102] |
| NR1H2 | LXRB | Liver X receptor β | CBIs [68, 70] oxysterols | no signal | M [68], T,B, prolfieration [102] |
| NR1H4 | FXR | Farnesoid x receptor | Bile acids | no signal | ND |
| NR1H5 | FXRB | Farnesoid x receptor β | Lanosterol | no signal | ND |
| NR1I1 | VDR | Vitamin D receptor | Vitamin D | Aβ/γδT, DC,M,S | Suppress B,DC,T cells [48] |
| NR1I2 | PXR | Pregnane X receptor | xenobiotics | no signal | IEC TLR expression [59] |
| NR1I3 | CAR | Constitutive androstane receptor | xenobiotics | no signal | ND |
| NR2A1 | HNF4A | Hepatocyte nuclear factor 4α | fatty acid [103] | SC, preT | ND |
| NR2A2 | HNF4G | Hepatocyte nuclear factor 4γ | orphan | S | ND |
| NR2B1 | RXRA | Retinoic X receptor α | 9-cis RA [104, 105] | γδT, M, | Pleiotropic |
| NR2B2 | RXRB | Retinoic X receptor β | 9-cis RA [104, 105] | no signal | Pleiotropic |
| NR2B3 | RXRG | Retinoic X receptor γ | 9-cis RA [104, 105] | ILC2 | Pleiotropic |
| NR2C1 | TR2 | Testicular receptor 2 | orphan | no signal | ND |
| NR2C2 | TR4 | Testicular receptor 4 | orphan | no signal | granulomas [66] |
| NR2E1 | TLX | Tailless | orphan | no signal | ND |
| NR2E3 | PNR | Photoreceptor nuclear receptor | orphan | ILCs? | ND |
| NR2F1 | COUP-TFI | COUP transcription factor 1 | orphan | S | ND |
| NR2F2 | COUP-TFII | COUP transcription factor 2 | orphan | S | Lymphatic vessel dev [62] |
| NR2F6 | EAR2 | ErbA-related protein 2 | orphan | weak signal | Th17 cells [49] |
| NR3A1 | ESR1 | Estrogen receptor 1 | estrogens | proB, preT, SC, S | Pleiotropic |
| NR3A2 | ESR2 | Estrogen receptor 2 | estrogens | weak signal | Pleiotropic |
| NR3B1 | ESRRA | Estrogen related receptor α | orphan | weak signal | Teff and Tmem [50] |
| NR3B2 | ESRRB | Estrogen related receptor β | orphan | weak signal | ND |
| NR3B3 | ESRRG | Estrogen related receptor γ | orphan | S | Fe load mac [57] |
| NR3C1 | GR | Glucocoticoid receptor | Glucocorticoid | broad | T cell dev [47] |
| NR3C2 | MLR | Mineralocorticoid receptor | Mineralocorticoid | B, DC, S | ND |
| NR3C3 | PGR | Progesterone receptor | Progesterone | B cells? | ND |
| NR3C4 | AR | Androgen receptor | androgens | γδT, ILC2, S | ND |
| NR4A1 | NGFIB | Nerve growth factor IB | orphan | DC,ILCs,M, S, T | T cells, M dev [51] [52, 53] |
| NR4A2 | NURR1 | Nuclear receptor related 1 | orphan | DC, ILCs, M, T | T cells dev [51] |
| NR4A3 | NOR1 | Neuron-derived orphan receptor 1 | orphan | DC, ILCs, M, T | T cells dev [51] |
| NR5A1 | SF1 | Steroidogenic factor 1 | Phosphatidyl inositols [63] | weak signal | Spleen dev [64, 65] |
| NR5A2 | LRH-1 | Liver receptor homolog-1 | Phosphatidyl inositols [63] | S | ND |
| NR6A1 | GCNF | Germ cell nuclear factor | orphan | weak signal | ND |
| NR0B1 | DAX-1 | DAX-1** | orphan | weak signal | ND |
| NR0B2 | SHP | small Heterodimer partner | orphan | SC, M | TLR signaling mac [54] |
a)
Human NHR classification from [1]. References added for natural ligands unknown in 2006. Classic NHRs (yellow boxes). Receptors with known accessory iLBPs (grey boxes). Receptors with broad specificity for ligands (brown boxes). Biological function of ligand unknown (red text). Examples of functions discussed in this review (blue boxes). Abreviations: M=myeloid cells, Ne=neutrophil, S=stroma, SC=stem cells, ND=no data, Reg=positive and negative modulation of function, dev=development, Teff=T effector cells, Tmem=T memory cells, mac=macrophage. FXRB is a pseudogene in the human lineage and a lanosterol receptor in mice [69].
b)
Gene symbol shared by human and mouse NHR.
c
Expression of NHRs in immune cells are from (http://www.immgen.org/index_content.html).