We recently reported that diabetes negates the cerebrovascular protection typically seen in adult female rats resulting in cognitive impairment, which is worsened by increased parenchymal bleeding and edema after ischemic stroke. Although women experience more severe diabetes and suffer from a higher rate of diabetic complications, including stroke and cognitive impairment, underlying mechanisms contributing to sex differences are limited. Emerging evidence suggests interleukin (IL)-17 contributes to cerebrovascular pathologies: (1) high salt diet-mediated expansion of IL-17-producing T cells (Th17) in the gut microbiome promotes cerebrovascular dysfunction and cognitive impairment in male mice, (2) increased IL-17-producing γδTCR cells exacerbates stroke injury in male mice, and (3) IL-17 promotes rupture of cerebral aneurysms in female mice. Based on these premises, we investigated the potential involvement of IL-17-producing inflammatory cells in cerebrovascular dysfunction and post-stroke vascular injury in diabetes by measuring intestinal, circulating, or cerebral T cell profiles as well as in plasma IL-17 in both sexes. Cell suspensions prepared from naive or stroked (3 days after stroke) diabetic and control rats were analyzed by flow cytometry, and IL-17 levels were measured in plasma using ELISA. Diabetes deferentially promoted the expansion of cerebral Th17 cells in females. In response to stroke, diabetes had a sexually dimorphic effect on the expansion of numerous T cell profiles. These results suggest that a better understanding of the role of IL-17-producing cells in diabetes may identify potential avenues in which the molecular mechanisms contributing to these sex differences can be further elucidated.

中文翻译：

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糖尿病中风促进 T 细胞的性别二态性扩张。


我们最近报道说，糖尿病会破坏成年雌性大鼠中常见的脑血管保护作用，导致认知障碍，而缺血性中风后脑实质出血和水肿增加会加剧认知障碍。尽管女性患有更严重的糖尿病，并且患糖尿病并发症（包括中风和认知障碍）的几率更高，但导致性别差异的潜在机制是有限的。新出现的证据表明白细胞介素 (IL)-17 会导致脑血管病变：(1) 高盐饮食介导的肠道微生物群中产生 IL-17 的 T 细胞 (Th17) 的扩增会促进雄性小鼠的脑血管功能障碍和认知障碍，(2 ) 产生 IL-17 的 γδTCR 细胞增加会加剧雄性小鼠的中风损伤，(3) IL-17 会促进雌性小鼠的脑动脉瘤破裂。基于这些前提，我们通过测量肠道、循环或大脑 T 细胞谱以及血浆 IL-17，研究了产生 IL-17 的炎症细胞在糖尿病脑血管功能障碍和中风后血管损伤中的潜在参与。性别。通过流式细胞术分析从幼稚或中风（中风后 3 天）糖尿病大鼠和对照大鼠制备的细胞悬液，并使用 ELISA 测量血浆中的 IL-17 水平。糖尿病会促进女性大脑 Th17 细胞的扩张。为了应对中风，糖尿病对大量 T 细胞谱的扩增产生了性别二态性影响。这些结果表明，更好地了解 IL-17 产生细胞在糖尿病中的作用可能会找到潜在的途径，进一步阐明导致这些性别差异的分子机制。