Sjögren's disease & overlap diseases
Mitochondrial-impaired ductal epithelium fuels tertiary lymphoid structure (TLS) formation in Sjögren’s disease
Authors' conclusion
Mitochondrial injury in SD epithelial cells emerges as a trigger of TLS formation and progressive autoimmunity in SjD.
Study context
- Population
- Labial salivary gland biopsies from Sjögren's disease (SjD) and non-SjD individuals; NOD/ShiLtj mice with spontaneous SjD
- Participants
- 848 labial salivary gland (LSG) biopsies
- Comparison
- SjD vs non-SjD labial salivary gland biopsies; nicotinamide mononucleotide to restore mitochondrial function in NOD/ShiLtj mice
- SjDn = 668
- non-SjDn = 180reference
Methodological detailsbulk transcriptomics, single cell RNA-sequencing (scRNA-seq), spatial transcriptomics, transmission electron microscopy, histology, in vivo validation in NOD/ShiLtj mice
- Bulk transcriptomics
- scRNA-seq
- Spatial transcriptomics
- Transmission electron microscopy
- Histology
- In vivo validation in NOD/ShiLtj mice
Main finding
As reported in the abstract
- Mitochondrial function impaired in LSG tissues from SjD patients
- In NOD/ShiLtj mice, nicotinamide mononucleotide attenuated ductal injury and reduced immune cell infiltration
- Each LSG cellular subset harbours a distinct mitochondrial transcriptional profile (molecular fingerprint)
- Striated duct cells most enriched with mitochondria among epithelial subtypes (transmission electron microscopy (TEM))
- Profound mitochondrial dysfunction and impaired oxidative phosphorylation in SjD LSGs, particularly with TLSs
- Proinflammatory SD subset SD-C1 (MMP7-marked) markedly expanded in SjD-TLS+ tissues, with severe mitochondrial impairment
- SD-C1 cells showed enhanced crosstalk with T cells, B cells and macrophages and colocalized with periductal immune aggregates where TLSs formed
Original publication
Mitochondrial-impaired ductal epithelium fuels TLS formation in Sjögren’s disease. Ann Rheum Dis. Published 5 June 2026. doi:10.
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