Back to Search
Start Over
OCA-B promotes autoimmune demyelination through control of stem-like CD4 + T cells.
- Source :
-
BioRxiv : the preprint server for biology [bioRxiv] 2024 Apr 17. Date of Electronic Publication: 2024 Apr 17. - Publication Year :
- 2024
-
Abstract
- Stem-like T cell populations can selectively contribute to autoimmunity, but the activities that promote and sustain these populations are incompletely understood. Here, we show that T cell-intrinsic loss of the transcription cofactor OCA-B protects mice from experimental autoimmune encephalomyelitis (EAE) while preserving responses to CNS infection. In adoptive transfer EAE models driven by multiple antigen encounters, OCA-B deletion nearly eliminates CNS infiltration, proinflammatory cytokine production and clinical disease. OCA-B-expressing CD4 <superscript>+</superscript> T cells within the CNS of mice with EAE comprise a minority of the population but display a memory phenotype and preferentially confer disease. In a relapsing-remitting EAE model, OCA-B T cell deficiency specifically protects mice from relapse. During remission, OCA-B promotes the expression of Tcf7 , Slamf6 , and Sell in proliferating T cell populations. At relapse, OCA-B loss results in both the accumulation of an immunomodulatory CD4 <superscript>+</superscript> T cell population expressing Ccr9 and Bach2 , and the loss of pro-inflammatory gene expression from Th17 cells. These results identify OCA-B as a driver of pathogenic stem-like T cells.
Details
- Language :
- English
- Database :
- MEDLINE
- Journal :
- BioRxiv : the preprint server for biology
- Accession number :
- 38076925
- Full Text :
- https://doi.org/10.1101/2023.11.29.569210