biostudies-literatureHoover PJNational Institute of Allergy and Infectious DiseasesNational Institute of Diabetes and Digestive and Kidney DiseasesNIDDK NIH HHSRheumatology Research FoundationLupus Research AllianceAccelerating Medicines Partnership Autoimmune and Immune-Mediated Diseases NetworkNational Institutes of HealthDepartment of DefenseNIH HHSe20241873https://www.ebi.ac.uk/biostudies/studies/S-EPMC12928530biostudies-literatureUnknown222(11)Monocytes and macrophages in patients with lupus nephritis exhibit altered behavior compared with healthy kidneys. How to optimally use mouse models to develop treatments targeting these cells is poorly understood. This study compared intrarenal myeloid cells in four mouse models and 155 lupus nephritis patients using single-cell profiling, spatial transcriptomics, and functional studies. Across mouse models, monocyte and macrophage subsets consistently expanded or contracted in disease. A subset of murine classical monocytes expanded in disease; these cells expressed Cd9, Spp1, Ctsd, Cd63, Apoe, and Trem2, genes associated with tissue injury in other organs that play roles in inflammation, lipid metabolism, and tissue repair. Resident macrophages expressed similar genes in clinical diseasThe Journal of experimental medicineA human-mouse atlas of intrarenal myeloid cells identifies conserved disease-associated macrophages in lupus nephritis.PMC12928530U01DK133081UH3DK114861UC2-AR081031UC2-DE032254124441515829669UC2-AR081025UC2-AR081023UH3DK114926R01 DK131482U24DK114886U01DK1149331R01DK131482-01A1UC2-AR081029U01DK133092U01DK133091U01DK133093U01DK133090R01 DK085241P01AI148102U01DK133113U01DK133095U01DK133097U01DK114907U01DK133768UC2-AR081039U01DK114908UC2-AR081034UH3DK114937UH3DK114915U01DK133766UC2-AR081032UC2-AR081033U01DK114866W81XWH-21-1-0966U01DK114920U01DK114923998677Wofsy DFew-Cooper TJDavidson ALederer JEisenhaure TRaychaudhuri SJames JGuthridge JBuyon JPAnolik JGoodman STuschl TBelmont HMKang JPeters MSimmons DBerthier CCJames JAIzmirly PMLieb DJLi SHacohen NMoreland LShah SIUtz PJBrenner MDonlin LHolers VMDiamond BKalunian KPetri MGuthridge JMArazi ASonny AIvashkiv LRaparia CAccelerating Medicines Partnership in RA/SLE networkShen-Orr SSMishra RFava AHodgin JBHoover PJClancy RMKamen DGregersen PBuyon JLeavitt RGurajala SSPutterman CTzur YBykerk VRobinson BfalseA human-mouse atlas of intrarenal myeloid cells identifies conserved disease-associated macrophages in lupus nephritis.Monocytes and macrophages in patients with lupus nephritis exhibit altered behavior compared with healthy kidneys. How to optimally use mouse models to develop treatments targeting these cells is poorly understood. This study compared intrarenal myeloid cells in four mouse models and 155 lupus nephritis patients using single-cell profiling, spatial transcriptomics, and functional studies. Across mouse models, monocyte and macrophage subsets consistently expanded or contracted in disease. A subset of murine classical monocytes expanded in disease; these cells expressed Cd9, Spp1, Ctsd, Cd63, Apoe, and Trem2, genes associated with tissue injury in other organs that play roles in inflammation, lipid metabolism, and tissue repair. Resident macrophages expressed similar genes in clinical diseas2025-01-01T00:00:00Z2025 Nov2026-07-16T18:35:04.322Z2026-07-11T03:08:40.902ZS-EPMC129285304090012410.1084/jem.20241873