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Macrophage heterogeneity in tissues: phenotypic diversity and functions

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      During development and throughout adult life, macrophages derived from hematopoietic progenitors are seeded throughout the body, initially in the absence of inflammatory and infectious stimuli as tissue-resident cells, with enhanced recruitment, activation, and local proliferation following injury and pathologic insults. We have learned a great deal about macrophage properties ex vivo and in cell culture, but their phenotypic heterogeneity within different tissue microenvironments remains poorly characterized, although it contributes significantly to maintaining local and systemic homeostasis, pathogenesis, and possible treatment. In this review, we summarize the nature, functions, and interactions of tissue macrophage populations within their microenvironment and suggest questions for further investigation.

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          Microglia are the resident macrophages of the central nervous system and are associated with the pathogenesis of many neurodegenerative and brain inflammatory diseases; however, the origin of adult microglia remains controversial. We show that postnatal hematopoietic progenitors do not significantly contribute to microglia homeostasis in the adult brain. In contrast to many macrophage populations, we show that microglia develop in mice that lack colony stimulating factor-1 (CSF-1) but are absent in CSF-1 receptor-deficient mice. In vivo lineage tracing studies established that adult microglia derive from primitive myeloid progenitors that arise before embryonic day 8. These results identify microglia as an ontogenically distinct population in the mononuclear phagocyte system and have implications for the use of embryonically derived microglial progenitors for the treatment of various brain disorders.

            Author and article information

            [1 ]Sir William Dunn School of Pathology, University of Oxford Oxford, UK
            [2 ]Nuffield Department of Primary Care Health Sciences, University of Oxford Oxford, UK
            [3 ]Botnar Research Centre, NDORMS, University of Oxford Oxford, UK
            Author notes
            Correspondence to:, Siamon Gordon, Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK, Tel.: +44 1865 275500, Fax: +44 1865 275515, e-mail: siamon.gordon@
            Immunol Rev
            Immunol. Rev
            Immunological Reviews
            John Wiley & Sons Ltd
            November 2014
            15 October 2014
            : 262
            : 1
            : 36-55
            © 2014 The Authors. Immunological Reviews published by John Wiley & Sons Ltd

            This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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