{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T21:11:44Z","timestamp":1779138704379,"version":"3.51.4"},"reference-count":39,"publisher":"American Society for Clinical Investigation","issue":"4","license":[{"start":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T00:00:00Z","timestamp":1740355200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"crossref","award":["P30 AR075043"],"award-info":[{"award-number":["P30 AR075043"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"crossref","award":["1K24AR077313"],"award-info":[{"award-number":["1K24AR077313"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,24]]},"abstract":"<jats:p>\n                    Necrobiosis is a histologic term used to describe abnormal deposits of \u201cdegenerating\u201d collagen within the skin. It can be found as an incidental finding in various granulomatous conditions, but is a hallmark of necrobiosis lipoidica (NL) and necrobiotic xanthogranuloma (NXG). There is limited prior research on necrobiosis. Here, we employed single-cell analysis of lesional and nonlesional skin to study the pathophysiology of necrobiosis. Our findings demonstrate that necrobiotic lesional skin is characterized by SPP1\n                    <jats:sup>hi<\/jats:sup>\n                    macrophages expressing\n                    <jats:italic>MARCO<\/jats:italic>\n                    ;\n                    <jats:italic>NKG7<\/jats:italic>\n                    -expressing effector CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells coexpressing\n                    <jats:italic>CCL5<\/jats:italic>\n                    ,\n                    <jats:italic>IFNG<\/jats:italic>\n                    ,\n                    <jats:italic>GZM<\/jats:italic>\n                    s, and\n                    <jats:italic>PRF1<\/jats:italic>\n                    ; CCL5\n                    <jats:sup>hi<\/jats:sup>\n                    fibroblasts coexpressing\n                    <jats:italic>CXCL9<\/jats:italic>\n                    , diverse collagens (e.g.,\n                    <jats:italic>COL4A4<\/jats:italic>\n                    ,\n                    <jats:italic>COL11A1<\/jats:italic>\n                    ,\n                    <jats:italic>COL8A1<\/jats:italic>\n                    ), and\n                    <jats:italic>TIMP1<\/jats:italic>\n                    ; and\n                    <jats:italic>IGHM<\/jats:italic>\n                    -expressing plasma cells. Integrative analysis of signaling ligands and receptor expression identified strong cell-cell communication between NKG7\n                    <jats:sup>+<\/jats:sup>\n                    T cells, CCL5\n                    <jats:sup>hi<\/jats:sup>\n                    fibroblasts, and SPP1-expressing macrophages. In contrast, these cell populations were not dominant features of systemic sclerosis, another collagen deposition disease. Furthermore, although SPP1-expressing macrophages were detectable in sarcoidosis,\n                    <jats:italic>IFNG<\/jats:italic>\n                    -expressing T cells were a more defining feature of sarcoidosis compared with NL and NXG. From these findings, we speculate that necrobiosis results from the deposition of diverse collagens and ECM proteins through a process driven by CCL5-expressing fibroblasts and SPP1-expressing macrophages.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.178766","type":"journal-article","created":{"date-parts":[[2025,2,23]],"date-time":"2025-02-23T14:00:45Z","timestamp":1740319245000},"source":"Crossref","is-referenced-by-count":2,"title":["SPP1hi macrophages, NKG7 T cells, CCL5hi fibroblasts, and IgM plasma cells are dominant features of necrobiosis"],"prefix":"10.1172","volume":"10","author":[{"given":"Stephanie T.","family":"Le","sequence":"first","affiliation":[{"name":"Department of Dermatology, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alina I.","family":"Marusina","sequence":"additional","affiliation":[{"name":"Department of Dermatology, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5735-7233","authenticated-orcid":true,"given":"Alexander A.","family":"Merleev","sequence":"additional","affiliation":[{"name":"Department of Dermatology, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Kirane","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California, Davis, Sacramento, California, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga","family":"Kruglinskaya","sequence":"additional","affiliation":[{"name":"Physioseq, Sacramento, California, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrey","family":"Kunitsyn","sequence":"additional","affiliation":[{"name":"Physioseq, Sacramento, California, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikolay Yu","family":"Kuzminykh","sequence":"additional","affiliation":[{"name":"Institute of Biochemical Physics, Russian Academy of Science, Moscow, Russia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4227-6868","authenticated-orcid":true,"given":"Xianying","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Dermatology,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie Y.","family":"Li","sequence":"additional","affiliation":[{"name":"Physioseq, Sacramento, California, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Liakos","sequence":"additional","affiliation":[{"name":"Department of Dermatology, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4006-8945","authenticated-orcid":true,"given":"J. 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