{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T01:15:26Z","timestamp":1790039726735,"version":"4.0.1"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T00:00:00Z","timestamp":1721952000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The CCL2\u2013CCR2 axis is involved in lupus nephritis, however the precise roles in the mechanisms by which different pathological lesions develop after glomerular immune complex deposition remain elusive. Previously, we demonstrated that genetic CCR2 inhibition induced a histological switch from glomerular endocapillary hypercellularity to wire\u2010loop lesions in murine lupus nephritis. This study aimed to clarify the CCL2\u2013CCR2 axis\u2010mediated cellular mechanism in the formation of these different pathological lesions. We injected MRL\/lpr mouse\u2010derived monoclonal IgG3 antibody\u2010producing hybridomas, 2B11.3 or B1, into wild\u2010type (WT) mice to selectively induce glomerular endocapillary hypercellularity or wire\u2010loop lesions. The expression of chemokine and chemokine receptors was analyzed using RT\u2010quantitative PCR and\/or immunofluorescence. We found 2B11.3 caused glomerular endocapillary hypercellularity in WT mice with glomerular infiltration of larger numbers of CCR2\u2010expressing macrophages and neutrophils phagocyting immune complex, whereas B1 induced wire\u2010loop lesions. In glomerular endocapillary hypercellularity, CCL2 was identified as the ligand involved in the CCR2\u2010positive cell infiltration; it was expressed by glomerular endothelial cells and macrophages. Notably, 2B11.3\u2010induced glomerular endocapillary hypercellularity converted to wire\u2010loop lesions with reduced glomerular macrophage and neutrophil infiltration in CCL2\u2010deficient (\n                    <jats:italic>Ccl2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice similarly observed in\n                    <jats:italic>C<\/jats:italic>\n                    <jats:italic>cr2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. Moreover, this histological conversion was also observed when both glomerular macrophage and neutrophil infiltration were inhibited in anti\u2010Ly6G antibody\u2010treated\n                    <jats:italic>Ccr<\/jats:italic>\n                    5\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice but not when only glomerular macrophage infiltration was inhibited in\n                    <jats:italic>Ccr5<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice or when only glomerular neutrophil infiltration was inhibited in anti\u2010Ly6G antibody\u2010treated WT mice. In contrast, B1 injection caused wire\u2010loop lesions in\n                    <jats:italic>Ccl2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    and\n                    <jats:italic>Ccr2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, as observed in WT mice. Moreover, 2B11.3 induced CCL2 from glomerular endothelial cells to a larger extent than B1 when injected into\n                    <jats:italic>Ccr2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. In conclusion, the CCL2\u2013CCR2 axis determines whether glomerular endocapillary hypercellularity or wire\u2010loop lesions develop by regulating glomerular infiltration of phagocytic cells: macrophages and neutrophils. \u00a9 2024 The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.6331","type":"journal-article","created":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T04:45:43Z","timestamp":1721969143000},"page":"174-185","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The\n                    <scp>CCL2<\/scp>\n                    \u2013\n                    <scp>CCR2<\/scp>\n                    axis determines whether glomerular endocapillary hypercellularity or wire\u2010loop lesions develop through glomerular macrophage and neutrophil infiltration in lupus nephritis"],"prefix":"10.1002","volume":"264","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9235-9798","authenticated-orcid":false,"given":"Takeshi","family":"Zoshima","sequence":"first","affiliation":[{"name":"Department of Nephrology and Rheumatology, Graduate School of Medical Sciences Kanazawa University  Kanazawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2161-2087","authenticated-orcid":false,"given":"Tomohisa","family":"Baba","sequence":"additional","affiliation":[{"name":"Division of Cancer and Senescent Biology, Cancer Research Institute Kanazawa University  Kanazawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimihiko","family":"Nakatani","sequence":"additional","affiliation":[{"name":"Department of Nephrology Kyoto Yamashiro General Medical Center  Kizugawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michio","family":"Nagata","sequence":"additional","affiliation":[{"name":"Kidney and Vascular Pathology, Faculty of Medicine University of Tsukuba  Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naofumi","family":"Mukaida","sequence":"additional","affiliation":[{"name":"Cancer Research Institute Kanazawa University  Kanazawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuhiro","family":"Kawano","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Rheumatology, Graduate School of Medical Sciences Kanazawa University  Kanazawa 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