Lupus & antiphospholipid syndrome
Spatially distinct macrophage subsets drive myofibroblast heterogeneity and maladaptive fibrosis in lupus nephritis
Authors' conclusion
Our data reveal a spatially and functionally heterogeneous landscape of macrophage-fibroblast crosstalk in LN.
Study context
- Population
- Human lupus nephritis (LN) biopsies and healthy controls (Accelerating Medicines Partnership-SLE cohort); spatial transcriptomics of biopsies from 6 patients with LN; mouse modelsspatial transcriptomics: 6 LN patients
- Participants
- 156 vs 30
- Comparison
- LN vs Healthy controls
- LNn = 156
- Healthy controlsn = 30reference
- Outcome
- Macrophage-fibroblast interactions in LN
Methodological detailssingle-cell RNA sequencing, spatial transcriptomics, in vitro coculture studies using mouse models
- Single-cell RNA sequencing
- Spatial transcriptomics
- In vitro coculture studies using mouse models
Main finding
As reported in the abstract
- 2 myofibroblast subsets identified: proinflammatory Myofib1 enriched in the tubulointerstitium and fibrotic/remodelling Myofib2 in glomeruli, both correlating with the histologic chronicity index
- Spatial transcriptomics: Myofib1 colocalised with activated resident macrophage (RM) subsets; Myofib2 with glomerular infiltrating disease-associated macrophages
- In vitro: nephritic RMs promote a proinflammatory, remodelling fibroblast phenotype that impairs wound healing and drives a Myofib1-like gene programme
- In vitro: disease-associated macrophages generated profibrotic fibroblasts with dysregulated reparative capacity
- Key ligand-receptor interactions: Spp1/integrins, Sema4/PlexinB, nicotinamide phosphoribosyl transferase/INSR
Original publication
Spatially distinct macrophage subsets drive myofibroblast heterogeneity and maladaptive fibrosis in lupus nephritis. Ann Rheum Dis. Published 13 August 2026. doi:10.
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