Single cell RNA sequencing of aqueous humour demonstrates the presence of long-lived Tissue Resident memory (cells) in the uveal tract of the human eye
Accept poster if oral is not possible ?
Yes
Purpose
Our purpose is to establish whether T cells are present in the human uvea and determine whether tissue resident memory TRM ( cells) might have a role in health, acute inflammation and in remission from uveitis
Methods
1.We profiled T cell subtypes in human post-mortem uveal tissue by spectral cytometry and immunofluorescence imaging. 2.We examined aqueous humour cells from 11 donors with active anterior uveitis of heterogeneous causes using single cell RNA & T cell receptor (TCR) sequencing. 3.Using bulk RNA sequencing and weighted gene co-expression network analysis (WGCNA) we studied iris tissue from 13 glaucoma donors ( 6 with a history of uveitis-in-remission and 7 without), undergoing trabeculectomy.
Results
1.We demonstrate that non-inflamed uveal tissue contains 17 T-cell subpopulations ( 7 clusters of CD8 T-cells, 5 clusters of CD4 T cells and 5 clusters of double-negative γδ and included T cell subtypes CD8+ CD103+ tissue resident memory T (TRM) cells.
2. 10 different T cell subtypes were identified in aqueous humour of subjects with anterior uveitis, with TEM/TRM cytotoxic T cells the most prevalent. 3, Bulk RNA sequencing and WCGNA analysis overlaid with single cell RNA showed an enrichment for activated T cell genes and TRM development in uveitis donors.
Conclusion
We suggest a contributory role for long-lived TRM cells in the pathophysiology of immune-mediated inflammatory diseases including in the eye from acute disease to remission.
Conflict of interest
No
1
Last name
SHARMA
Initials of first name(s)
SM
Department
Kennedy Institute of Rheumatology, University of Oxford
City
Oxford
Country
United Kingdom
2
Last name
Foers
Initials of first name(s)
AD
Department
Kennedy Institute of Rheumatology, University of Oxford
City
Oxford
Country
United Kingdom
3
Last name
Reekie
Initials of first name(s)
IR
Department
Kennedy Institute of Rheumatology, University of Oxford
City
Oxford
Country
United Kingdom
4
Last name
Buckley
Initials of first name(s)
TW
Department
Oxford Eye Hospital, John Radcliffe Hospital
City
Oxford
Country
United Kingdom
5
Last name
Attar
Initials of first name(s)
M
Department
Kennedy Institute of Rheumatology, University of Oxford
City
Oxford
Country
United Kingdom
6
Last name
Aguilar-Munoa
Initials of first name(s)
S
Department
4National Institute for Health Research (NIHR) Biomedical Research Centre, Moorfields Eye Hospital N
City
London
Country
United Kingdom
7
Last name
Pilapil
Initials of first name(s)
Q
Department
Oxford Eye Hospital, John Radcliffe Hospital
City
Oxford
Country
United Kingdom
8
Last name
Wickramasinghe
Initials of first name(s)
L
Department
Kennedy Institute of Rheumatology, University of Oxford
City
Oxford
Country
United Kingdom
9
Last name
Abdalla
Initials of first name(s)
MEA
Department
Oxford Eye Hospital, John Radcliffe Hospital
City
Oxford
Country
United Kingdom
10
Last name
Pledger
Initials of first name(s)
S
Department
Kennedy Institute of Rheumatology, University of Oxford
City
Oxford
Country
United Kingdom
11
Last name
Sansom
Initials of first name(s)
SN
Department
Kennedy Institute of Rheumatology, University of Oxford
City
Oxford
Country
United Kingdom
12
Last name
Sherlock
Initials of first name(s)
JP
Department
Kennedy Institute of Rheumatology, University of Oxford
City
Oxford
Country
United Kingdom
13
Last name
Buckley
Initials of first name(s)
CD
Department
Kennedy Institute for Rheumatology, University of Oxford
City
Oxford
Country
United Kingdom
This website uses cookies to ensure you get the best experience on our website.
Learn more