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 (T_regs) 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⁺ T_regs. 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 (T_H17) and T_H1 cells. Aspirin also increased the transcription of Il11 mediated by the transcription factor CREB, which was necessary for the generation of T_regs. Neutralization of IL-11 negated the effects of aspirin on T_reg development and exacerbated EAE. Furthermore, we found that IL-11 alone was sufficient to maintain the percentage of FoxP3⁺ T_regs and protect mice from EAE. These results identify a previously uncharacterized mode of action of aspirin.

多发性硬化症（MS）是一种人类疾病，由靶向中枢神经系统表达的髓磷脂蛋白的自身免疫性T细胞引起。在MS中，表达FoxP3的调节性T细胞（T _regs减少），这有助于自身反应性T细胞的活化。因为阿司匹林（乙酰水杨酸）是使用最广泛的非甾体类抗炎药，所以我们检查了其在患有实验性自身免疫性脑脊髓炎（EAE）（MS的动物模型）的小鼠中的免疫调节作用。我们发现小剂量阿司匹林在复发和慢性疾病小鼠模型中均抑制了EAE的临床症状。阿司匹林减少了由髓磷脂碱性蛋白（MBP）特异性T细胞以及相关的血管周围套囊，炎症和脱髓鞘作用驱动的EAE的发展。阿司匹林的作用需要CD25 ⁺ FoxP3 ⁺ T _{regs的存在}。阿司匹林增加了T细胞中Foxp3和白介素4（IL-4）的含量，并抑制了幼稚T细胞向T辅助17（T _H 17）和T _H 1细胞的分化。阿司匹林还增加了由转录因子CREB介导的Il11的转录，这是产生T _regs所必需的。IL-11的中和作用消除了阿司匹林对_Treg发育的影响，并加剧了EAE。此外，我们发现单独使用IL-11足以维持FoxP3 ⁺ T _regs的百分比并保护小鼠免受EAE侵害。这些结果确定了阿斯匹林以前未知的作用方式。