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This CD11B\n                    <jats:sup>hi<\/jats:sup>\n                    F4\/80\n                    <jats:sup>int<\/jats:sup>\n                    Ly-6C\n                    <jats:sup>lo<\/jats:sup>\n                    macrophage subset was most abundant in livers during maximal fibrosis resolution and represented the principle matrix metalloproteinase (MMP) -expressing subset. Depletion of this population in\n                    <jats:italic>CD11B<\/jats:italic>\n                    promoter\u2013diphtheria toxin receptor (CD11B-DTR) transgenic mice caused a failure of scar remodeling. Adoptive transfer and in situ labeling experiments showed that these restorative macrophages derive from recruited Ly-6C\n                    <jats:sup>hi<\/jats:sup>\n                    monocytes, a common origin with profibrotic Ly-6C\n                    <jats:sup>hi<\/jats:sup>\n                    macrophages, indicative of a phenotypic switch in vivo conferring proresolution properties. Microarray profiling of the Ly-6C\n                    <jats:sup>lo<\/jats:sup>\n                    subset, compared with Ly-6C\n                    <jats:sup>hi<\/jats:sup>\n                    macrophages, showed a phenotype outside the M1\/M2 classification, with increased expression of MMPs, growth factors, and phagocytosis-related genes, including Mmp9, Mmp12, insulin-like growth factor 1 (Igf1), and Glycoprotein (transmembrane) nmb (Gpnmb). Confocal microscopy confirmed the postphagocytic nature of restorative macrophages. Furthermore, the restorative macrophage phenotype was recapitulated in vitro by the phagocytosis of cellular debris with associated activation of the ERK signaling cascade. Critically, induced phagocytic behavior in vivo, through administration of liposomes, increased restorative macrophage number and accelerated fibrosis resolution, offering a therapeutic strategy to this orphan pathological process.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1119964109","type":"journal-article","created":{"date-parts":[[2012,10,25]],"date-time":"2012-10-25T20:21:47Z","timestamp":1351196507000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":922,"title":["Differential Ly-6C expression identifies the recruited macrophage phenotype, which orchestrates the regression of murine liver fibrosis"],"prefix":"10.1073","volume":"109","author":[{"given":"Prakash","family":"Ramachandran","sequence":"first","affiliation":[{"name":"University of Edinburgh\/Medical Research Council Centre for Inflammation Research and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Pellicoro","sequence":"additional","affiliation":[{"name":"University of Edinburgh\/Medical Research Council Centre for Inflammation Research and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine A.","family":"Vernon","sequence":"additional","affiliation":[{"name":"University of Edinburgh\/Medical Research Council Centre for Inflammation Research and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"Boulter","sequence":"additional","affiliation":[{"name":"University of Edinburgh\/Medical Research Council Centre for Inflammation Research and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca L.","family":"Aucott","sequence":"additional","affiliation":[{"name":"University of Edinburgh\/Medical Research Council Centre for Inflammation Research and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aysha","family":"Ali","sequence":"additional","affiliation":[{"name":"University of Edinburgh\/Medical Research Council Centre for Inflammation Research and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen N.","family":"Hartland","sequence":"additional","affiliation":[{"name":"University of Edinburgh\/Medical Research Council Centre for Inflammation Research and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria K.","family":"Snowdon","sequence":"additional","affiliation":[{"name":"University of Edinburgh\/Medical Research Council Centre for Inflammation Research and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Cappon","sequence":"additional","affiliation":[{"name":"University of Edinburgh\/Medical Research Council Centre for Inflammation Research and"},{"name":"Department of Surgical, Oncological and Gastroenterological Sciences, Padova University Hospital, 35128 Padova, Italy; 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