Macrophages, the most plastic cells of the haematopoietic system, are found in all tissues and show great functional diversity. They have roles in development, homeostasis, tissue repair and immunity. Although tissue macrophages are anatomically distinct from one another, and have different transcriptional profiles and functional capabilities, they are all required for the maintenance of homeostasis. However, these reparative and homeostatic functions can be subverted by chronic insults, resulting in a causal association of macrophages with disease states. In this Review, we discuss how macrophages regulate normal physiology and development, and provide several examples of their pathophysiological roles in disease. We define the ‘hallmarks’ of macrophages according to the states that they adopt during the performance of their various roles, taking into account new insights into the diversity of their lineages, identities and regulation. It is essential to understand this diversity because macrophages have emerged as important therapeutic targets in many human diseases.
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The authors apologize to colleagues whose papers they were unable to cite on this occasion. T.A.W. is supported by the intramural research program of the National Institutes of Allergy and Infectious Diseases (National Institutes of Health (NIH)). This work was supported by the National Cancer Institute of the NIH (award numbers R01CA131270S, U54HD058155 and PO1CA100324 (to J.W.P.), and HL076746, DK094641 and DK094641 (to A.C.)); the Diabetes Family Fund (to the University of California, San Francisco), an American Heart Association (AHA) Innovative Award (12PILT11840038) and a NIH Director’s Pioneer Award (DP1AR064158 to A.C.).
The authors declare no competing financial interests.
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Wynn, T., Chawla, A. & Pollard, J. Macrophage biology in development, homeostasis and disease. Nature 496, 445–455 (2013). https://doi.org/10.1038/nature12034
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