Spatially resolved transcriptomics reveals pro-inflammatory fibroblast involved in lymphocyte recruitment through CXCL8 and CXCL10

Abstract

The interplay among different cells in a tissue is essential for maintaining homeostasis. Although, disease states have been traditionally attributed to individual cell types, increasing evidence and new therapeutic options have demonstrated the primary role of multicellular functions to understand health and disease, opening new avenues to understand pathogenesis and develop new treatment strategies. We recently described the cellular composition and dynamics of the human oral mucosa; however, the spatial arrangement of cells is needed to better understand a morphologically complex tissue. Here, we link single-cell RNA sequencing, spatial transcriptomics, and high-resolution multiplex fluorescence in situ hybridisation to characterise human oral mucosa in health and oral chronic inflammatory disease. We deconvolved expression for resolution enhancement of spatial transcriptomic data and defined highly specialised epithelial and stromal compartments describing location-specific immune programs. Furthermore, we spatially mapped a rare pathogenic fibroblast population localised in a highly immunogenic region, responsible for lymphocyte recruitment through CXCL8 and CXCL10 and with a possible role in pathological angiogenesis through ALOX5AP. Collectively, our study provides a comprehensive reference for the study of oral chronic disease pathogenesis.

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All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided

The following data sets were generated

Article and author information

Author details

  1. Ana J Caetano

    Centre for Craniofacial and Regenerative Biology, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  2. Yushi Redhead

    Centre for Craniofacial and Regenerative Biology, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  3. Farah Karim

    Centre for Craniofacial and Regenerative Biology, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  4. Pawan Dhami

    NIHR BRC Genomics Centre, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  5. Shichina Kannambath

    NIHR BRC Genomics Centre, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  6. Rosamond Nuamah

    NIHR BRC Genomics Centre, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  7. Ana A Volponi

    Centre for Craniofacial and Regenerative Biology, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5661-0807
  8. Luigi Nibali

    Department of Periodontology, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  9. Veronica Booth

    Department of Periodontology, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  10. Eleanor M D'Agostino

    Unilever, Sharnbrook, United Kingdom
    Competing interests
    Eleanor M D'Agostino, is an employee of Unilever Plc.. The authors state no conflict of interest.
  11. Paul T Sharpe

    Centre for Craniofacial and Regenerative Biology, King's College London, London, United Kingdom
    For correspondence
    paul.sharpe@kcl.ac.uk
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2116-9561

Funding

BBSRC (BB/P504506/1)

  • Ana J Caetano

NIHR Biomedical Research Centre Guy's and St Thomas' NHS Foundation Trust and King's College London

  • Paul T Sharpe

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Bian Zhuan, Wuhan University, China

Version history

  1. Received: June 30, 2022
  2. Preprint posted: July 5, 2022 (view preprint)
  3. Accepted: January 16, 2023
  4. Accepted Manuscript published: January 17, 2023 (version 1)
  5. Version of Record published: February 3, 2023 (version 2)

Copyright

© 2023, Caetano et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Ana J Caetano
  2. Yushi Redhead
  3. Farah Karim
  4. Pawan Dhami
  5. Shichina Kannambath
  6. Rosamond Nuamah
  7. Ana A Volponi
  8. Luigi Nibali
  9. Veronica Booth
  10. Eleanor M D'Agostino
  11. Paul T Sharpe
(2023)
Spatially resolved transcriptomics reveals pro-inflammatory fibroblast involved in lymphocyte recruitment through CXCL8 and CXCL10
eLife 12:e81525.
https://doi.org/10.7554/eLife.81525

Share this article

https://doi.org/10.7554/eLife.81525

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