Multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) are neuroinflammatory conditions where inflammatory CD4⁺ T cells play a major role. Forkhead box P3 (Foxp3)⁺ regulatory T (Treg) cells suppress inflammation and an increase in their numbers and activity is beneficial for MS and EAE. However, studies have shown that Treg cells can transdifferentiate to pathogenic Th17 cells under inflammatory conditions. Drugs that stimulate Treg cell induction and their resistance to inflammatory stimuli are necessary to develop effective therapies to treat MS. Here, we show that primaquine (PQ), an anti-malarial drug, suppresses EAE through the stimulation of Foxp3⁺ Treg cells. PQ-elicited Treg cells are refractory to inflammatory stimuli and suppress EAE. Additionally, PQ-elicited Foxp3⁺ Treg cells were more efficient in suppressing the proliferation of responder cells compared to PBS-elicited Treg cells. Although PQ does not directly induce Foxp3⁺ Treg cell differentiation from naïve T cells, it modulated dendritic cells (DCs) to induce Foxp3⁺ Treg cells in an indoleamine 2,3 dioxygenase (IDO)-dependent manner. Together, our results show that PQ elicits Foxp3⁺ Treg cells with a superior suppressive activity to reduce EAE. PQ has the potential as a safe and effective treatment for MS and other CNS autoimmune inflammatory diseases.

多发性硬化症 (MS) 和实验性自身免疫性脑脊髓炎 (EAE) 是神经炎性疾病，其中炎性 CD4 ⁺ T 细胞起主要作用。Forkhead box P3 (Foxp3) ⁺调节性 T (Treg) 细胞抑制炎症，其数量和活性的增加有利于 MS 和 EAE。然而，研究表明，Treg 细胞可以在炎症条件下转分化为致病性 Th17 细胞。刺激 Treg 细胞诱导及其对炎症刺激的抵抗力的药物是开发治疗 MS 的有效疗法所必需的。在这里，我们展示了伯氨喹 (PQ)，一种抗疟疾药物，通过刺激 Foxp3 ^{+ 来}抑制 EAETreg 细胞。PQ 引发的 Treg 细胞对炎症刺激具有抵抗力并抑制 EAE。此外，与 PBS 引发的 Treg 细胞相比，PQ 引发的 Foxp3 ⁺ Treg 细胞在抑制应答细胞增殖方面更有效。虽然 PQ 不直接诱导 Foxp3 ⁺ Treg 细胞从初始 T 细胞分化，但它调节树突细胞 (DC) 以吲哚胺 2,3 双加氧酶 (IDO) 依赖性方式诱导 Foxp3 ⁺ Treg 细胞。总之，我们的结果表明 PQ 诱导 Foxp3 ⁺ Treg 细胞具有卓越的抑制活性以减少 EAE。PQ 有可能成为治疗 MS 和其他 CNS 自身免疫性炎症疾病的安全有效方法。