Molecular and spatial analysis of tertiary lymphoid structures in Sjogren’s syndrome

Saba Nayar, Jason D. Turner, Saba Asam, Eanna Fennell, Matthew Pugh, Serena Colafrancesco, Onorina Berardicurti, Charlotte G. Smith, Joe Flint, Ana Teodosio, Valentina Iannizzotto, David H. Gardner, Joel Roon, Ilya Korsunsky, Dawn Howdle, Andreas P. Frei, Kara G. Lassen, Simon J. Bowman, Wan-Fai Ng, Adam P. Croft, Andrew Filer, Benjamin A. Fisher, Christopher D. Buckley and Francesca Barone ()
Additional contact information
Saba Nayar: University of Birmingham
Jason D. Turner: University of Birmingham
Saba Asam: University of Birmingham
Eanna Fennell: University of Limerick
Matthew Pugh: University of Birmingham
Serena Colafrancesco: Humanitas University
Onorina Berardicurti: Università Campus Bio-Medico, Rome, and Immunorheumatology Unit, Fondazione Policlinico Universitario Campus Bio Medico
Charlotte G. Smith: University of Birmingham
Joe Flint: University of Birmingham
Ana Teodosio: University of Birmingham
Valentina Iannizzotto: University of Birmingham
David H. Gardner: University of Birmingham
Joel Roon: Utrecht University
Ilya Korsunsky: Brigham and Women’s Hospital
Dawn Howdle: University of Birmingham
Andreas P. Frei: Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd
Kara G. Lassen: Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd
Simon J. Bowman: University of Birmingham
Wan-Fai Ng: University College Cork
Adam P. Croft: University of Birmingham
Andrew Filer: University of Birmingham
Benjamin A. Fisher: University of Birmingham
Christopher D. Buckley: University of Birmingham
Francesca Barone: University of Birmingham

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract Tertiary lymphoid structures play important roles in autoimmune and non-autoimmune conditions. While many of the molecular mechanisms involved in tertiary lymphoid structure formation have been identified, the cellular sources and temporal and spatial relationship remain unknown. Here we use combine single-cell RNA-sequencing, spatial transcriptomics and proteomics of minor salivary glands of patients with Sjogren’s disease and Sicca Syndrome, with ex-vivo functional studies to construct a cellular and spatial map of key components involved in the formation and function of tertiary lymphoid structures. We confirm the presence of a fibroblast cell state and identify a pericyte/mural cell state with potential immunological functions. The identification of cellular properties associated with these structures and the molecular and functional interactions identified by this analysis may provide key therapeutic cues for tertiary lymphoid structures associated conditions in autoimmunity and cancer.

Date: 2025
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DOI: 10.1038/s41467-024-54686-0

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