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Perivascular macrophages in health and disease


Macrophages are a heterogeneous group of cells that are capable of carrying out distinct functions in different tissues, as well as in different locations within a given tissue. Some of these tissue macrophages lie on, or close to, the outer (abluminal) surface of blood vessels and perform several crucial activities at this interface between the tissue and the blood. In steady-state tissues, these perivascular macrophages maintain tight junctions between endothelial cells and limit vessel permeability, phagocytose potential pathogens before they enter tissues from the blood and restrict inappropriate inflammation. They also have a multifaceted role in diseases such as cancer, Alzheimer disease, multiple sclerosis and type 1 diabetes. Here, we examine the important functions of perivascular macrophages in various adult tissues and describe how these functions are perturbed in a broad array of pathological conditions.

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C.E.L. thanks Yorkshire Cancer Research, Prostate Cancer UK, Breast Cancer Now and the European Commission (MSCA-ITN-2015-ETN, project acronym ‘ISPIC’; and H2020-MSCA-RISE-2018, project acronym ‘Cancer’) for grant support of her work in this area. A.L. thanks Yorkshire Cancer Research for its support of his current work on perivascular macrophages in cancer. M.D.P. acknowledges grant support from the Swiss National Science Foundation (31003A-165963), Swiss Cancer League (KFS-3759-08-2015) and European Research Council (EVOLVE_725051).

Reviewer information

Nature Reviews Immunology thanks G. Faracco, L. Iruela-Arispe and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Author information

A.L. and C.E.L. conceived the topic. All authors provided intellectual input and contributed to writing, reviewing and editing the article.

Competing interests

The authors declare no competing interests.

Correspondence to Claire E. Lewis.


Stria vascularis

A highly vascularized area in the lateral wall of the cochlea (a sensory organ of the inner ear) that produces endolymph and is responsible for generating the endocochlear potential that is required for the transduction of sound.

Blood–brain barrier

(BBB). A tightly regulated, protective, vascular interface that separates the peripheral blood and central nervous system.

Alternative (M2) macrophage activation

Activation to a group of polarized, anti-inflammatory phenotypes (M2a, M2b and M2c) that is induced by type 2 cytokines such as IL-4 and IL-13 (M2a), immune complexes and Toll-like receptor or IL-1 receptor ligands (M2b), and IL-10 and glucocorticoids (M2c).

Classical (M1) macrophage activation

Activation to a polarized, pro-inflammatory and antimicrobial phenotype that is induced by the type 1 cytokine interferon-γ, various microbial molecules (such as lipopolysaccharide) or other inflammatory cytokines (such as tumour necrosis factor and granulocyte–macrophage colony-stimulating factor).

Islets of Langerhans

Regions of the pancreas that contain the hormone-producing cells.

Reticuloendothelial system

A network of cells sharing a common function, namely, phagocytosis.

Bowman capsule

A cup-like sac at the beginning of the tubular component of a nephron in the mammalian kidney that encloses a cluster of microscopic blood vessels known as the glomerulus and filters the blood to form urine.

Dense core granules

Subcellular organelles in the β-cells of the pancreatic islets that store and release various peptide hormones, including insulin.

Subcapsular sinus

The space between the capsule and the cortex of a lymph node that enables the free movement of lymphatic fluid.


Capillaries with a fenestrated, discontinuous endothelium.

Seminiferous tubules

Structures in the testis that contain epithelium enveloping and supporting germ cells that are undergoing progressive differentiation and development into mature spermatozoa.

Leydig cells

Cells in the connective tissue between the seminiferous tubules that produce testosterone.

Corpus luteum

A temporary, hormone-secreting structure that develops in an ovary after an ovum has been discharged at ovulation.


Movement of cells through a basement membrane into a blood or lymphatic vessel.

Clodronate-containing liposomes

(CCLs). Synthesized liposomes containing the bisphosphonate clodronate, which kills macrophages when taken up by them.

Cerebral amyloid angiopathy

A condition in which β-amyloid is deposited around the small-sized and mid-sized arteries (and, sometimes, the veins) of the cerebral cortex.

Experimental autoimmune uveitis

A mouse or rat model of inflammation in the uveal component of the eye caused by an autoimmune reaction to self antigens.

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Further reading

Fig. 1: Interactions between perivascular macrophages and blood vessels in steady-state tissues.
Fig. 2: Role of perivascular macrophages in diseased tissues.