Compositional variation in eye-infiltrating immune cells distinguishes human uveitis subtypes
Summary: Uveitis is a heterogeneous group of ocular inflammatory diseases that respond inadequately to empiric therapy, underscoring the need to define pathophysiologic subtypes. Toward this goal, we applied single-cell transcriptional and immune receptor profiling to ocular fluid biopsies from 23 p...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-03-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225001889 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850026336345653248 |
|---|---|
| author | Christian Concepcion Yu Xia Yulia Korshunova Gregory W. Bligard Amal Taylor Michael A. Paley Philip A. Ruzycki Lynn M. Hassman |
| author_facet | Christian Concepcion Yu Xia Yulia Korshunova Gregory W. Bligard Amal Taylor Michael A. Paley Philip A. Ruzycki Lynn M. Hassman |
| author_sort | Christian Concepcion |
| collection | DOAJ |
| description | Summary: Uveitis is a heterogeneous group of ocular inflammatory diseases that respond inadequately to empiric therapy, underscoring the need to define pathophysiologic subtypes. Toward this goal, we applied single-cell transcriptional and immune receptor profiling to ocular fluid biopsies from 23 patients with diverse clinical features. We found that a subset of ocular T cells undergoes local clonal expansion, indicating that antigens trigger uveitis in some patients. Infiltrates from HLA-B27 associated acute anterior uveitis (HLA-B27 AAU) were enriched in myeloid cells and innate immune signaling pathways, while chronic uveitis featured prominent adaptive immune cells and transcriptional programs, indicating that immunologic features distinguish uveitis subtypes. Clinical features including anatomic involvement were associated with additional variability in the immune cell profile. These insights highlight the potential for deep transcriptional profiling of ocular immune cells to reveal endotypes within uveitis. |
| format | Article |
| id | doaj-art-9840f0eccc3c49c6a220cf26c4f1c75d |
| institution | DOAJ |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-9840f0eccc3c49c6a220cf26c4f1c75d2025-08-20T03:00:35ZengElsevieriScience2589-00422025-03-0128311192810.1016/j.isci.2025.111928Compositional variation in eye-infiltrating immune cells distinguishes human uveitis subtypesChristian Concepcion0Yu Xia1Yulia Korshunova2Gregory W. Bligard3Amal Taylor4Michael A. Paley5Philip A. Ruzycki6Lynn M. Hassman7Department of Ophthalmology, University of Colorado, Aurora, CO 80045, USA; Department of Ophthalmology and Visual Sciences, Washington University in St. Louis, St. Louis, MO 63108, USADepartment of Ophthalmology and Visual Sciences, Washington University in St. Louis, St. Louis, MO 63108, USADepartment of Ophthalmology and Visual Sciences, Washington University in St. Louis, St. Louis, MO 63108, USADepartment of Ophthalmology and Visual Sciences, Washington University in St. Louis, St. Louis, MO 63108, USADepartment of Ophthalmology and Visual Sciences, Washington University in St. Louis, St. Louis, MO 63108, USADepartment of Medicine, Washington University in St. Louis, St. Louis, MO 63108, USADepartment of Ophthalmology and Visual Sciences, Washington University in St. Louis, St. Louis, MO 63108, USADepartment of Ophthalmology, University of Colorado, Aurora, CO 80045, USA; Department of Ophthalmology and Visual Sciences, Washington University in St. Louis, St. Louis, MO 63108, USA; Corresponding authorSummary: Uveitis is a heterogeneous group of ocular inflammatory diseases that respond inadequately to empiric therapy, underscoring the need to define pathophysiologic subtypes. Toward this goal, we applied single-cell transcriptional and immune receptor profiling to ocular fluid biopsies from 23 patients with diverse clinical features. We found that a subset of ocular T cells undergoes local clonal expansion, indicating that antigens trigger uveitis in some patients. Infiltrates from HLA-B27 associated acute anterior uveitis (HLA-B27 AAU) were enriched in myeloid cells and innate immune signaling pathways, while chronic uveitis featured prominent adaptive immune cells and transcriptional programs, indicating that immunologic features distinguish uveitis subtypes. Clinical features including anatomic involvement were associated with additional variability in the immune cell profile. These insights highlight the potential for deep transcriptional profiling of ocular immune cells to reveal endotypes within uveitis.http://www.sciencedirect.com/science/article/pii/S2589004225001889Cell biologyImmunityTranscriptomics |
| spellingShingle | Christian Concepcion Yu Xia Yulia Korshunova Gregory W. Bligard Amal Taylor Michael A. Paley Philip A. Ruzycki Lynn M. Hassman Compositional variation in eye-infiltrating immune cells distinguishes human uveitis subtypes iScience Cell biology Immunity Transcriptomics |
| title | Compositional variation in eye-infiltrating immune cells distinguishes human uveitis subtypes |
| title_full | Compositional variation in eye-infiltrating immune cells distinguishes human uveitis subtypes |
| title_fullStr | Compositional variation in eye-infiltrating immune cells distinguishes human uveitis subtypes |
| title_full_unstemmed | Compositional variation in eye-infiltrating immune cells distinguishes human uveitis subtypes |
| title_short | Compositional variation in eye-infiltrating immune cells distinguishes human uveitis subtypes |
| title_sort | compositional variation in eye infiltrating immune cells distinguishes human uveitis subtypes |
| topic | Cell biology Immunity Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225001889 |
| work_keys_str_mv | AT christianconcepcion compositionalvariationineyeinfiltratingimmunecellsdistinguisheshumanuveitissubtypes AT yuxia compositionalvariationineyeinfiltratingimmunecellsdistinguisheshumanuveitissubtypes AT yuliakorshunova compositionalvariationineyeinfiltratingimmunecellsdistinguisheshumanuveitissubtypes AT gregorywbligard compositionalvariationineyeinfiltratingimmunecellsdistinguisheshumanuveitissubtypes AT amaltaylor compositionalvariationineyeinfiltratingimmunecellsdistinguisheshumanuveitissubtypes AT michaelapaley compositionalvariationineyeinfiltratingimmunecellsdistinguisheshumanuveitissubtypes AT philiparuzycki compositionalvariationineyeinfiltratingimmunecellsdistinguisheshumanuveitissubtypes AT lynnmhassman compositionalvariationineyeinfiltratingimmunecellsdistinguisheshumanuveitissubtypes |