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Understanding the interplay between immune cells and stromal cells is needed to develop effective therapeutic strategies. Here, we investigated the landscape of macrophage-fibroblast interactions in human LN and validated these findings in mouse models.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    We characterized distinct fibroblast subsets and their interactions with renal macrophages using single-cell RNA sequencing (scRNAseq) of 156 human LN biopsies and 30 healthy controls from the AMP-SLE cohort, and spatial transcriptomics of biopsies from 6 LN patients.\n                    <jats:italic>In vitro<\/jats:italic>\n                    co-culture studies using mouse models were performed to further define functional consequences of these interactions.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    We identified two myofibroblast subsets: a pro-inflammatory subset (Myofib1) enriched in the tubulointerstitium, and a fibrotic\/remodeling subset (Myofib2) in glomeruli, both correlating with the histologic chronicity index. Spatial transcriptomics revealed different colocalization patterns, with Myofib1 interacting with activated resident macrophage (RM) subsets and Myofib2 with glomerular infiltrating disease-associated macrophages.\n                    <jats:italic>In vitro<\/jats:italic>\n                    co-culture studies demonstrated that nephritic RMs promote a pro-inflammatory, remodeling fibroblast phenotype that impairs wound healing and drives a Myofib1-like gene program, whereas disease-associated macrophages generated profibrotic fibroblasts with dysregulated reparative capacity. Cell-cell communication analyses identified key ligand-receptor interactions mediating this crosstalk, including Spp1\/integrins, Sema4\/PlexinB, and NAMPT\/INSR.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our data reveal a spatially and functionally heterogeneous landscape of macrophage-fibroblast crosstalk in LN. These findings advance our understanding of renal fibrogenesis in LN, highlighting specific fibro-inflammatory circuits that may represent therapeutic targets to prevent chronic renal damage.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.04.27.719870","type":"posted-content","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T17:35:18Z","timestamp":1777570518000},"source":"Crossref","is-referenced-by-count":3,"title":["Spatially Distinct Macrophage Subsets Drive Myofibroblast Heterogeneity and Maladaptive Fibrosis in Lupus Nephritis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5361-1257","authenticated-orcid":false,"given":"Chirag","family":"Raparia","sequence":"first","affiliation":[{"name":"The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA"},{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5343-429X","authenticated-orcid":false,"given":"Paul","family":"Hoover","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junting","family":"Ai","sequence":"additional","affiliation":[{"name":"University of Chicago, Chicago, Illinois, USA,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Clark","sequence":"additional","affiliation":[{"name":"University of Chicago, Chicago, Illinois, USA,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujal","family":"Shah","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Accelerating Medicines Partnership (AMP) RA\/SLE Network","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3250-3804","authenticated-orcid":false,"given":"Betty","family":"Diamond","sequence":"additional","affiliation":[{"name":"The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nir","family":"Hacohen","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard, Cambridge, MA, USA,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnon","family":"Arazi","sequence":"additional","affiliation":[{"name":"The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4081-6464","authenticated-orcid":false,"given":"Anne","family":"Davidson","sequence":"additional","affiliation":[{"name":"The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026050409551062000_2026.04.27.719870v1.1","first-page":"1432","article-title":"Risk of End-Stage Renal Disease in Patients With Lupus Nephritis, 1971-2015: A Systematic Review and Bayesian Meta-Analysis","volume":"68","year":"2016","journal-title":"Arthritis & rheumatology (Hoboken, N.J.)"},{"key":"2026050409551062000_2026.04.27.719870v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-05769-3"},{"key":"2026050409551062000_2026.04.27.719870v1.3","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/s41581-022-00590-z","article-title":"The fibrogenic niche in kidney fibrosis: components and mechanisms","volume":"18","year":"2022","journal-title":"Nature reviews. 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