Research ArticleImmunology

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

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Science Signaling  27 Nov 2018:
Vol. 11, Issue 558, eaar8278
DOI: 10.1126/scisignal.aar8278

Aspirin protects Tregs

Aspirin is a common pain reliever that inactivates the enzyme cyclooxygenase, which is required for the synthesis of inflammatory prostaglandins and thromboxane. Mondal et al. found that aspirin also reduced the development of disease in mice with experimental autoimmune encephalitis (EAE), a model of multiple sclerosis (MS), by reversing the depletion of regulatory T cells (Tregs) that occurs during the disease. The effects of aspirin required the cytokine IL-11, which was itself sufficient to promote Treg stability and protect the mice from EAE development. These data suggest that low-dose aspirin regimens may benefit patients with MS.


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

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