Language

English

Publication Date

1-1-2026

Journal

Frontiers in Immunology

DOI

10.3389/fimmu.2026.1797691

PMID

41939878

PMCID

PMC13044039

PubMedCentral® Posted Date

3-19-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Background: Sjögren's Disease (SjD) is a chronic autoimmune condition characterized by lymphocytic infiltration of lacrimal glands (LG) and salivary glands (SG). In SG, these immune structures have properties of ectopic lymphoid structures (ELS) and appear to play a critical role in disease pathology. While the presence of ELS in patients' SG biopsies is linked to disease severity, their presence and composition in LG has not been well characterized.

Methods: The properties and time course of apparent ELS development in LG from the male non-obese diabetes free (NOR) sub-strain of the Non-Obese Diabetic (NOD) mice was investigated at stages encompassing early to advanced lymphocytic infiltration. LG ELS were characterized morphologically by histology and immunofluorescence. Changes in LG gene expression were determined for genes involved in ELS formation and maturation, LG homeostasis and LG apoptosis.

Results: LG ELS were characterized by segregation of B and T cell zones and the presence of high endothelial venules, follicular dendritic centers, GL7+ germinal center B cells, and IgG producing plasma cells. Gene expression data showed early upregulation of ELS indicators such as Ltb, Glycam1, Cxcl13, Cxcr5, Ccl19 and Ccr7 while other components showed elevation at later stages (Aicda and Il21). Increased Fasl and decreased Gpx4 expression suggested glandular apoptosis and ferroptosis concomitant with ELS formation.

Conclusion: ELS form spontaneously in the LG of the male NOR mouse model of SjD and can recapitulate features of secondary lymphoid organs potentially acting as drivers of autoimmunity to sustain local glandular disease.

Keywords

Animals, Sjogren's Syndrome, Disease Models, Animal, Mice, Lacrimal Apparatus, Mice, Inbred NOD, Male, Tertiary Lymphoid Structures, Disease Progression, Apoptosis, apoptosis, autoimmune disease, ferroptosis, lacrimal gland, secondary lymphoid organs, Sjögrens disease, ectopic lymphoid structures

Published Open-Access

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