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Using a technical advance in spatial transcriptomics, we generated a spatially resolved, single-cell resolution atlas of kidney tissue from eight patients with cLN and four control individuals. Annotated cells were assigned to 30 reference cell types, including major kidney subsets and infiltrating immune cells. Analysis of spatial distribution demonstrated that individual immune lineages localized to specific regions in cLN kidneys, including myeloid cells that trafficked to inflamed glomeruli and B cells that clustered within tubulointerstitial immune hotspots. Gene expression varied as a function of tissue location, demonstrating how incorporation of spatial data can provide new insights into the immunopathogenesis of SLE. Alterations in immune phenotypes were accompanied by parallel changes in gene expression by resident kidney stromal cells. However, there was little correlation between histologic scoring of cLN disease activity and glomerular cell transcriptional signatures at the level of individual glomeruli. Last, we identified modules of spatially correlated gene expression with predicted roles in induction of inflammation and the development of tubulointerstitial fibrosis. Single-cell spatial transcriptomics allowed insights into the molecular heterogeneity of cLN, paving the way toward more targeted and personalized treatment approaches.<\/jats:p>","DOI":"10.1126\/scitranslmed.adl1666","type":"journal-article","created":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T14:00:34Z","timestamp":1732716034000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":49,"title":["Childhood-onset lupus nephritis is characterized by complex interactions between kidney stroma and infiltrating immune cells"],"prefix":"10.1126","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2844-5883","authenticated-orcid":true,"given":"Patrick","family":"Danaher","sequence":"first","affiliation":[{"name":"Bruker Spatial Biology, Seattle, WA 98109, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4563-5152","authenticated-orcid":true,"given":"Nicholas","family":"Hasle","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2798-6581","authenticated-orcid":true,"given":"Elizabeth D.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195, USA."},{"name":"Seattle Children\u2019s Research Institute, Seattle, WA 98101, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0976-5697","authenticated-orcid":true,"given":"Jordan E.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195, USA."},{"name":"Seattle Children\u2019s Research Institute, Seattle, WA 98101, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Rosenwasser","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195, USA."},{"name":"Seattle Children\u2019s Research Institute, Seattle, WA 98101, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7396-4335","authenticated-orcid":true,"given":"Christian","family":"Rickert","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3969-6597","authenticated-orcid":true,"given":"Elena W. 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