Gut microbiota transfer from autoimmune dry eye mice imprints stereotypic B cell receptor repertoires in the lacrimal gland and induces disease

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Abstract
Gut microbiota and humoral immunity have been suggested as key players in the pathogenesis of Sjögren disease (SjD), but their mechanisms remain unclear. In this study, we transferred the gut microbiota of SjD-like autoimmune dry eye disease model mice to B6 mice, then characterized the resulting gut microbiome composition, clinical ocular phenotype, and B cell receptor (BCR) repertoire. Notable changes were observed in the gut microbiome of NOD-FMT mice, accompanied by SjD-like clinical features, including elevated corneal fluorescein staining scores, reduced tear production, increased IL-6 mRNA levels, and decreased MUC5AC mRNA levels. Additionally, stereotypic B cell receptor (BCR) clonotypes were shared at significantly higher frequencies in NOD-FMT mice than in controls. The majority of B cell clones encoding these stereotypic clonotypes developed and expanded locally in the lacrimal gland, and some also achieved systemic presence. These results uncover a gut–ocular immune axis in which microbiota transfer induces stereotyped, systemically disseminating BCR clonotypes that contribute to the immunopathogenesis of autoimmune dry eye disease.
Funding Information
  • National Research Foundation of Korea (NRF-2022R1A2C3005472)
  • Korea Health Industry Development Institute (HI23C0521)
  • Ministry of Science and ICT, South Korea
  • Ministry of Health and Welfare
  • Ministry of Trade, Industry and Energy
  • Seoul National University
  • Seoul National University Hospital

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