Psychological stress has adverse effects on various human diseases, including those of the cardiovascular system. However, the mechanisms by which stress influences disease activity remain unclear. Here, using vaso-occlusive episodes (VOEs) of sickle cell disease as a vascular disease model, we show that stress promotes VOEs by eliciting a glucocorticoid hormonal response that augments gut permeability, leading to microbiota-dependent interleukin-17A (IL-17A) secretion from T helper 17 (Th17) cells of the lamina propria, followed by the expansion of the circulating pool of aged neutrophils that trigger VOEs. We identify segmented filamentous bacteria as the commensal essential for the stress-induced expansion of aged neutrophils that enhance VOEs in mice. Importantly, the inhibition of glucocorticoids synthesis, blockade of IL-17A, or depletion of the Th17 cell-inducing gut microbiota markedly reduces stress-induced VOEs. These results offer potential therapeutic targets to limit the impact of psychological stress on acute vascular occlusion.

心理压力对各种人类疾病都有不利影响，包括心血管系统疾病。然而，压力影响疾病活动的机制仍不清楚。在这里，使用镰状细胞病的血管闭塞发作 (VOE) 作为血管疾病模型，我们表明压力通过引发糖皮质激素激素反应来增加肠道通透性，从而导致微生物群依赖性白细胞介素 17A (IL-17A)从固有层的 T 辅助 17 (Th17) 细胞分泌，随后老化中性粒细胞的循环池扩大，触发 VOE。我们将分段的丝状细菌鉴定为压力诱导的衰老中性粒细胞扩张所必需的共生菌，从而增强小鼠的 VOE。重要的是，抑制糖皮质激素合成，阻断 IL-17A，或耗尽诱导 Th17 细胞的肠道微生物群显着降低了应激诱导的 VOE。这些结果提供了潜在的治疗目标，以限制心理压力对急性血管闭塞的影响。