Back to Search
Start Over
Single-cell sequencing of the retina shows that LDHA regulates pathogenesis of autoimmune uveitis.
- Source :
-
Journal of Autoimmunity . Feb2024, Vol. 143, pN.PAG-N.PAG. 1p. - Publication Year :
- 2024
-
Abstract
- Autoimmune uveitis (AU) is a severe disorder causing poor vision and blindness. However, the cellular dynamics and pathogenic mechanisms underlying retinal injury in uveitis remain unclear. In this study, single-cell RNA sequencing of the retina and cervical draining lymph nodes in experimental autoimmune uveitis mice was conducted to identify the cellular spatiotemporal dynamics and upregulation of the glycolysis-related gene LDHA. Suppression of LDHA can rescue the imbalance of T effector (Teff) cells/T regulator (Treg) cells under inflammation via downregulation of the glycolysis-PI3K signaling circuit and inhibition of the migration of CXCR4+ Teff cells towards retinal tissue. Furthermore, LDHA and CXCR4 are upregulated in the peripheral blood mononuclear cells of Vogt-Koyanagi-Harada patients. The LDHA inhibitor suppresses CD4+ T cell proliferation in humans. Therefore, our data indicate that the autoimmune environment of uveitis regulates Teff cell accumulation in the retina via glycolysis-associated LDHA. Modulation of this target may provide a novel therapeutic strategy for treating AU. • Glycolysis-associated LDHA promotes inflammation in uveitis. • LDHA promotes glycolysis-PI3K loop to induce Teff/Treg cells imbalance in uveitis. • LDHA fuels CXCR4+ Teff cells trafficking towards retina. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08968411
- Volume :
- 143
- Database :
- Academic Search Index
- Journal :
- Journal of Autoimmunity
- Publication Type :
- Academic Journal
- Accession number :
- 176270022
- Full Text :
- https://doi.org/10.1016/j.jaut.2023.103160