title: Macrophage heterogeneity in the context of rheumatoid arthritis.
abstract: Macrophages are very important in the pathogenesis of rheumatoid arthritis (RA). The increase in the number of sublining macrophages in the synovium is an early hallmark of active rheumatic disease, and high numbers of macrophages are a prominent feature of inflammatory lesions. The degree of synovial macrophage infiltration correlates with the degree of joint erosion, and depletion of these macrophages from inflamed tissue has a profound therapeutic benefit. Research has now uncovered an unexpectedly high level of heterogeneity in macrophage origin and function, and has emphasized the role of environmental factors in their functional specialization. Although the heterogeneous populations of macrophages in RA have not been fully characterized, preliminary results in mouse models of arthritis have contributed to our understanding of the phenotype and ontogeny of synovial macrophages, and to deciphering the properties of monocyte-derived infiltrating and tissue-resident macrophages. Elucidating the molecular mechanisms that drive polarization of macrophages towards proinflammatory or anti-inflammatory phenotypes could lead to identification of signalling pathways that inform future therapeutic strategies.
authors.affiliation: Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Oxford OX3 7LF, UK.
authors.forename: Irina A
authors.initials: IA
authors.lastname: Udalova
authors.affiliation: Humanitas Clinical and Research Centre and Humanitas University, via Manzoni 56, 20089 Rozzano, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
authors.affiliation: Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Oxford OX3 7LF, UK.
authors.forename: Marc
authors.initials: M
authors.lastname: Feldmann
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D002454:Cell Differentiation; D055808:Drug Discovery; D005786:Gene Expression Regulation; D006410:Hematopoiesis; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D058990:Molecular Targeted Therapy; D009000:Monocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D011518:Proto-Oncogene Proteins; D013583:Synovial Membrane / Q000473:pathology*; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1