Journal
ISCIENCE
Volume 26, Issue 5, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.isci.2023.106628
Keywords
-
Categories
Ask authors/readers for more resources
This study investigated the role of CD4+FoxP3+ regulatory T cells (Tregs) in regulating neuroinflammation during viral Ag-challenge and rechallenge. The findings show that Tregs recruited into mouse brains following prime-CNS boost displayed altered phenotypes and inefficient immunosuppressive capacity after repeated Ag-challenge. Treatment with amphiregulin (Areg) reduced the production of neurotoxic mediators and decreased microglial activation and proliferation. Overall, these data suggest that brain Tregs fail to control reactive gliosis in response to repeated Ag-challenge.
This study was undertaken to investigate the role of CD4+FoxP3+ regulatory T cells (Tregs) in regulating neuroinflammation during viral Ag-challenge and rechallenge. CD8(+) lymphocytes persisting within tissues are designated tissue-resident memory T cells (T-RM), within brain: bT(RM). Reactivation of bT(RM) with T cell epitope peptides generates rapid antiviral recall, but repeated stimulation leads to cumulative dysregulation of microglial activation, proliferation, and prolonged neurotoxic mediator production. Here, we show Tregs were recruited into murine brains following prime-CNS boost, but displayed altered phenotypes following repeated Ag-challenge. In response to repeated Ag, brain Tregs (bTregs) displayed inefficient immunosuppressive capacity, along with reduced expression of suppression of tumorigenicity 2 (ST2) and amphiregulin ( Areg). Ex vivo Areg treatment revealed reduced production of neurotoxic mediators such as iNOS, IL-6, and IL-1 beta, and decreased microglial activation and proliferation. Taken together, these data indicate bTregs display an unstable phenotype and fail to control reactive gliosis in response to repeated Ag-challenge.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available