Table 1. Distinct locations and functions of tissue macrophages.
Tissue | aCell type | bFunctions & notes | Phenotypic markers (cTissue-selective transcriptional regulators) |
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Adipose tissue | ‘Adipose-associated macrophages’ | Involved in control of insulin sensitivity96 and adaptive thermogenesis99. | F4/80+, CD45+ (white and brown adipose tissue)99 (PPARγ96) |
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Blood | Ly-6Clo monocytes | These monocytes function analogously as “intravascular housekeepers” clearing endothelial cell debris115. | CX3CR1+, Ly-6Clo, F4/80+, CSF1R+ 115 (Nr4a1115) |
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Bone | Osteoclasts | Multinucleated cells formed by fusion that resorb bone by disruption of the mineralized matrix36. | Calcitonin receptor+ (multinucleate)117 |
Bone marrow macrophages | Supporting erythropoeisis87, 88. Maintenance of hematopoietic stem cells in stem cell niches116. An independent self-renewing population30. | CD169+, F4/80+, ER-HR3+ 118 | |
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Central nervous system | Microglia | Promotes neuronal survival, front-line immune-surveillance cell, removal of dead neurons, synaptic remodelling76, 119. Derived from yolk sac and maintained and during inflammation independently of the bone marrow 15, 26, 65. | F4/80+, CD11b+, CD45lo 120 |
Perivascular macrophages | Immune surveillance. | F4/80+, CD11b+, CD163+, CD45hi 120 | |
Meningeal macrophages | Immune surveillance120. | F4/80+, CD11b+, CD45hi 120 | |
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Gastrointestinal tract | Intestinal macrophages | Maintenance of intestinal homeostasis and regulation of immune responses to commensals23, 121. | CX3CR1hi, F4/80+, CD11b+, CD11c+, CD64+ 121 |
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Liver | Kupffer cells (sessile) | Clearance of microorganisms and cell debris from the blood. Clearance of aged erythrocytes91, 122. Pre-natal origins22. Maintained in the adult independently of the bone marrow17 | F4/80hi, CD11blo, CD169+, CD68+, Galectin-3+123,dCD80lo/− 122 (PPARδ98) |
Motile liver macrophages | Immune surveilance122 | F4/80+, CD11b+, CD80hi 122 | |
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Lung | Alveolar macrophages | Immune-surveillance of the lung for inhaled pathogens51, homeostatic regulation of tissue function72, 124, for example clearance of surfactant. Prenatal origins22. Maintained in adult and during inflammation independently of the bone marrow30, 125. | F4/80lo, CD11blo, CD11chi, CD68+, Siglec F+, MARCO+, CD206+, Dectin-1+127, Galectin-3+ 123 (PPARγ72) |
Interstitial macrophages | Regulates DC maturation/activation126. | F4/80+, CD11c−, CD68+, MHCII+ 126 | |
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Serosal tissues | Peritoneal macrophages: F4/80hi majority | Immune surveillance and regulation of homeostatic environment50, 128. Apoptotic cell clearance80. Pre-natal origins22. Maintained in adult and during inflammation independently of the bone marrow22, 29. | F4/80hi, CD11bhi, dTim4+ 83 MHCIIlo |
F4/80lo Pleural macrophages: |
Immune surveillance129. | F4/80lo, CD11b+, Tim4−, MHCIIhi, CD11c+/− (This population is most likely heterogeneous, mixed with dendritic cells) | |
F4/80hi majority | Maintained in adult and can expand during TH2 inflammation independently of the bone marrow41 | F4/80hi, CD11bhi, dTim4+ | |
F4/80lo | F4/80lo, CD11b+, Tim4− (Dendritic cell-macrophage content undetermined, unpublished phenotypic observations) | ||
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Skin | Dermal macrophages | Immune surveillance130. | F4/80+, CD11b+, CD11clo, CD206+, MHCIIlo, CD169+ (In the deep dermis)123, Dectin-1+, CD301+ 132, Dectin-2+ 133 |
Langerhans cells | Interaction with T lymphocytes131. Derived from yolk sac and/or fetal liver and maintained independently of the bone marrow14, 16. | F4/80+, CD11b+, CD11c+, Langerin+ 14 (Id2134, Runx3135) | |
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Spleen | Marginal zone macrophages | Immune surveillance of the circulation102. | CD68+, CD209b+, MARCO+, Dectin-2+ 133, Tim4+ 109. (LXRα109) |
Metallophilic macrophages | Immune surveillance102. | CD68+, CD169+ 102 (LXRα109) | |
Red-pulp macrophages | Erythrocyte clearance and iron metabolism103. Pre-natal origins17, 22. Maintained in adult independently of the bone marrow30. | F4/80+, CD206+, Dectin-2+ 133 (Spi-C103) | |
White pulp (tingible body) macrophages | Clearance of apoptotic cells resulting during the germinal center reaction100. | CD68+ 102 |
This table represents a simplification and marked heterogeneity is evident in many tissues (for example, bone marrow, peritoneum, lung and liver) highlighted through fate mapping studies and phenotypic variation17, 22, 33, 122, 128.
Origin indicated only where experimentally established.
Select examples of tissue selective transcriptional regulators involved in cellular development or function are indicated.
Marker is expressed by the majority of the indicated cells. Subsets are only listed where distinct anatomical localization, function or origins are reported, and not those that are simply defined by variation in select receptor/antigen expression.