.png){kind=icon}
.png){kind=icon}
Return
MOG-Peptide Synergizes With Rapamycin to Drive CD4+ T Cells Into Protective Antigen-Specific Tregs in EAE
.png){kind=icon}
PRE
AI
M
T
A
R
S
S
M
J
M
L
S
J
DOI：10.1111/imm.70158.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
During multiple sclerosis, immune responses directed against myelin oligodendrocyte glycoprotein (MOG) contribute to demyelination and neuroinflammation. Among these, Th17 cells play an important role in promoting inflammatory damage to the myelin sheath and disrupting the integrity of blood brain barrier fibres. Despite advances in immunotherapy, there is no vaccine or durable cure for the disease. Regulatory T cells (Tregs) play a protective role against Th17-mediated damage of myelin sheath. In this study, we investigated whether rapamycin, a well-characterized mTOR inhibitor known to favour differentiation and metabolic reprogramming of Tregs, could synergize with MOG35-55-peptide to convert naïve T cells into protective, MOG35-55-specific Tregs. To test this, mice were immunized with a combination of NOAEL (No Observed Adverse Effect Level) dose of MOG35-55 and rapamycin. Remarkably, upon subsequent challenge with a disease-inducing (morbific) dose of MOG35-55, the immunized animals showed pronounced resistance to clinical symptoms of experimental autoimmune encephalomyelitis (EAE). While the unimmunized group showed severe EAE symptoms. Notably, there was a significant increase in the population of memory Tregs that primarily expressed an immunosuppressive phenotype (FoxP3+, TGF-β+, IL-10+). This was accompanied by a decline in Th17 cells. Additionally, a substantial increase in the pool of myeloid-derived suppressor cells (MDSCs) was observed in the rapamycin treated group, further contributing immunoregulatroy landscape. The underlying mechanism of this phenomenon was associated with the modulation of autophagic pathways by rapamycin, encouraging the differentiation of naïve CD4 T cells into MOG35-55-specific Tregs, as evidenced by tetramer staining. These findings provide a conceptual framework for exploring strategies aimed at promoting antigen-specific tolerance in autoimmune diseases.
Keywords:
autoimmune diseases
EAE
MOG
rapamycin
Tregs
Journal
IF:
5
Papers:
251
Citations:
1.3W
Organization
Cited Papers