Aspirin ameliorates experimental autoimmune encephalomyelitis through interleukin-11-mediated protection of regulatory T cells.

摘要: Multiple sclerosis (MS) is a human disease that results from autoimmune T cells targeting myelin protein expressed within the central nervous system. In MS, number of FoxP3-expressing regulatory (Tregs) reduced, which facilitates activation autoreactive cells. Because aspirin (acetylsalicylic acid) most widely used nonsteroidal anti-inflammatory drug, we examined its immunomodulatory effect in mice with experimental encephalomyelitis (EAE), an animal model MS. We found low-dose suppressed clinical symptoms EAE mouse models both relapsing-remitting and chronic disease. Aspirin reduced development driven by basic (MBP)-specific associated perivascular cuffing, inflammation, demyelination. The effects required presence CD25+FoxP3+ Tregs increased amounts Foxp3 interleukin-4 (IL-4) differentiation naive into helper 17 (TH17) TH1 also transcription Il11 mediated factor CREB, was necessary for generation Neutralization IL-11 negated on Treg exacerbated EAE. Furthermore, alone sufficient to maintain percentage FoxP3+ protect These identify previously uncharacterized mode action aspirin.