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Peer-reviewedCC BY 4.0Frontiers in Immunology

Single-cell sequencing of non-infectious and viral uveitis defines distinct mechanisms in ocular inflammation

  • Andrei Belean1
  • Shiori Kuramoto2
  • Isabel Risch1
  • Lynn M. Hassman3
  • Atsunobu Takeda4
  • Koh-Hei Sonoda2
  • Nobuyo Yawata5
  • Nicholas C. Borcherding6
  • Michael A. Paley1,6,7
7 affiliations
  1. 1Department of Medicine, Washington University School of Medicine
  2. 2Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University
  3. 3Department of Ophthalmology, University of Colorado Anschutz
  4. 4Department of Ophthalmology, Faculty of Medicine, Oita University
  5. 5Graduate School of Medical Sciences, Ocular Pathology and Imaging Science, Kyushu University
  6. 6Department of Pathology and Immunology, Washington University School of Medicine
  7. 7Department of Ophthalmology and Visual Sciences, Washington University School of Medicine
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Abstract

Introduction: Intraocular inflammation can arise from various conditions and can lead to severe vision loss and blindness. The differences in the intraocular immune response between infectious and autoimmune etiologies have not been defined.

Methods: Here we use single-cell RNA sequencing to compare the innate and adaptive immune response across 73 ocular and blood samples from 35 individuals with viral uveitis, autoimmune uveitis, or non-ocular inflammatory disease.

Results: This atlas suggests that viral uveitis is dominated by an influx of myeloid cells that activate cytotoxic CD8 T cells via antigen presentation, while in autoimmune uveitis, dendritic cells appear to activate both type 17 and regulatory CD4 T cells. Paired VDJ sequencing revealed that, while T-cell differentiation is modulated by etiology, B cells initiate similar responses between autoimmune and viral uveitis but differ by the degree of clonal expansion and somatic hypermutation.

Discussion: Collectively, these data identify the differences in innate and adaptive immune responses based on the intraocular stimulus.

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Cite

BibTeXRIS
BibTeX
@article{belean2026singlecell,
  title = {{Single-cell sequencing of non-infectious and viral uveitis defines distinct mechanisms in ocular inflammation}},
  author = {Andrei Belean and Shiori Kuramoto and Isabel Risch and Lynn M. Hassman and Atsunobu Takeda and Koh-Hei Sonoda and Nobuyo Yawata and Nicholas C. Borcherding and Michael A. Paley},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1916535},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1916535/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Single-cell sequencing of non-infectious and viral uveitis defines distinct mechanisms in ocular inflammation
AU  - Andrei Belean
AU  - Shiori Kuramoto
AU  - Isabel Risch
AU  - Lynn M. Hassman
AU  - Atsunobu Takeda
AU  - Koh-Hei Sonoda
AU  - Nobuyo Yawata
AU  - Nicholas C. Borcherding
AU  - Michael A. Paley
PY  - 2026
DA  - 2026/10/08
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1916535
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1916535/full
AB  - Introduction: Intraocular inflammation can arise from various conditions and can lead to severe vision loss and blindness. The differences in the intraocular immune response between infectious and autoimmune etiologies have not been defined.  Methods: Here we use single-cell RNA sequencing to compare the innate and adaptive immune response across 73 ocular and blood samples from 35 individuals with viral uveitis, autoimmune uveitis, or non-ocular inflammatory disease.  Results: This atlas suggests that viral uveitis is dominated by an influx of myeloid cells that activate cytotoxic CD8 T cells via antigen presentation, while in autoimmune uveitis, dendritic cells appear to activate both type 17 and regulatory CD4 T cells. Paired VDJ sequencing revealed that, while T-cell differentiation is modulated by etiology, B cells initiate similar responses between autoimmune and viral uveitis but differ by the degree of clonal expansion and somatic hypermutation.  Discussion: Collectively, these data identify the differences in innate and adaptive immune responses based on the intraocular stimulus.
SN  - 1664-3224
ER  -