Molecular and spatial analysis of tertiary lymphoid structures in Sjogren’s syndrome
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 us...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54686-0 |
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| author | 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 van Roon Ilya Korsunsky Dawn Howdle Roche Fibroblast Network Consortium Andreas P. Frei Kara G. Lassen Simon J. Bowman Wan-Fai Ng Adam P. Croft Andrew Filer Benjamin A. Fisher Christopher D. Buckley Francesca Barone |
| author_facet | 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 van Roon Ilya Korsunsky Dawn Howdle Roche Fibroblast Network Consortium Andreas P. Frei Kara G. Lassen Simon J. Bowman Wan-Fai Ng Adam P. Croft Andrew Filer Benjamin A. Fisher Christopher D. Buckley Francesca Barone |
| author_sort | Saba Nayar |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e5237692c7df49199440c51673881525 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-e5237692c7df49199440c516738815252025-01-05T12:40:01ZengNature PortfolioNature Communications2041-17232025-01-0116111710.1038/s41467-024-54686-0Molecular and spatial analysis of tertiary lymphoid structures in Sjogren’s syndromeSaba Nayar0Jason D. Turner1Saba Asam2Eanna Fennell3Matthew Pugh4Serena Colafrancesco5Onorina Berardicurti6Charlotte G. Smith7Joe Flint8Ana Teodosio9Valentina Iannizzotto10David H. Gardner11Joel van Roon12Ilya Korsunsky13Dawn Howdle14Roche Fibroblast Network ConsortiumAndreas P. Frei15Kara G. Lassen16Simon J. Bowman17Wan-Fai Ng18Adam P. Croft19Andrew Filer20Benjamin A. Fisher21Christopher D. Buckley22Francesca Barone23Rheumatology Research Group, Department of Inflammation and Ageing, College of Medicine & Health, University of BirminghamRheumatology Research Group, Department of Inflammation and Ageing, College of Medicine & Health, University of BirminghamRheumatology Research Group, Department of Inflammation and Ageing, College of Medicine & Health, University of BirminghamSchool of Medicine & HRI & Bernal Institute, University of LimerickDepartment of Immunology and Immunotherapy, College of Medicine & Health, University of BirminghamDepartment of Biomedical Sciences, Humanitas UniversityRheumatology, Immunology and Clinical Medicine Unit, Department of Medicine, Università Campus Bio-Medico, Rome, and Immunorheumatology Unit, Fondazione Policlinico Universitario Campus Bio MedicoRheumatology Research Group, Department of Inflammation and Ageing, College of Medicine & Health, University of BirminghamBirmingham Tissue Analytics, College of Medicine & Health, University of BirminghamBirmingham Tissue Analytics, College of Medicine & Health, University of BirminghamRheumatology Research Group, Department of Inflammation and Ageing, College of Medicine & Health, University of BirminghamBirmingham Tissue Analytics, College of Medicine & Health, University of BirminghamDepartment of Rheumatology & Clinical Immunology/Laboratory of Translational Immunology, University Medical Centre Utrecht, Utrecht UniversityCenter for Data Sciences, Brigham and Women’s HospitalBirmingham Tissue Analytics, College of Medicine & Health, University of BirminghamRoche Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche LtdRoche Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche LtdRheumatology Research Group, Department of Inflammation and Ageing, College of Medicine & Health, University of BirminghamHRB Clinical Research Facility, University College CorkRheumatology Research Group, Department of Inflammation and Ageing, College of Medicine & Health, University of BirminghamRheumatology Research Group, Department of Inflammation and Ageing, College of Medicine & Health, University of BirminghamRheumatology Research Group, Department of Inflammation and Ageing, College of Medicine & Health, University of BirminghamRheumatology Research Group, Department of Inflammation and Ageing, College of Medicine & Health, University of BirminghamRheumatology Research Group, Department of Inflammation and Ageing, College of Medicine & Health, University of BirminghamAbstract 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.https://doi.org/10.1038/s41467-024-54686-0 |
| spellingShingle | 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 van Roon Ilya Korsunsky Dawn Howdle Roche Fibroblast Network Consortium Andreas P. Frei Kara G. Lassen Simon J. Bowman Wan-Fai Ng Adam P. Croft Andrew Filer Benjamin A. Fisher Christopher D. Buckley Francesca Barone Molecular and spatial analysis of tertiary lymphoid structures in Sjogren’s syndrome Nature Communications |
| title | Molecular and spatial analysis of tertiary lymphoid structures in Sjogren’s syndrome |
| title_full | Molecular and spatial analysis of tertiary lymphoid structures in Sjogren’s syndrome |
| title_fullStr | Molecular and spatial analysis of tertiary lymphoid structures in Sjogren’s syndrome |
| title_full_unstemmed | Molecular and spatial analysis of tertiary lymphoid structures in Sjogren’s syndrome |
| title_short | Molecular and spatial analysis of tertiary lymphoid structures in Sjogren’s syndrome |
| title_sort | molecular and spatial analysis of tertiary lymphoid structures in sjogren s syndrome |
| url | https://doi.org/10.1038/s41467-024-54686-0 |
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