Central Laboratory, The First Hospital of Jilin University, Changchun, China.
Key Laboratory of Organ Regeneration and Transplantation, Ministry of Education, Changchun, China.
Front Immunol. 2020 Apr 22;11:687. doi: 10.3389/fimmu.2020.00687. eCollection 2020.
Myeloid-derived suppressor cells (MDSC) play a crucial role in regulating the intestinal immune response during colitis. We previously revealed an essential role of MDSC in promoting TH17 cell polarization, which was found to be arginase-1 (Arg-1)-dependent; however, the underlying mechanism remains obscure. Here we report that percentage of MDSC decreased in Arg mice during DSS-induced colitis. IL-17A levels reduced but IL-17F levels increased significantly in the colorectum of Arg mice, leading to severe tissue damage and high risk of mortality rate. Activation of estrogen receptor (ESR) increased pSTAT3 level in MDSC and consequently led to elevated percentage of MDSC and more Arg-1 and inducible nitric oxide synthase expression in MDSC. Increased level of IL-17A and reduced level of IL-17F alleviated colitis in mice consequently. Together, these findings demonstrate a protective role of MDSC-derived Arg-1 during colitis after activates ESR/STAT3 signaling in MDSC. High level of Arg-1 favors accumulation of IL-17A, but reduced IL-17F expression in the colorectum of mice and ultimately leading to relief of colitis, indicating a potential clinical impact of MDSC-derived Arg-1 for controlling inflammatory bowel disease.
髓系来源的抑制细胞 (MDSC) 在结肠炎期间调节肠道免疫反应中发挥着关键作用。我们之前揭示了 MDSC 在促进 TH17 细胞极化中的重要作用，这被发现是依赖于精氨酸酶-1（Arg-1）的；然而，其潜在机制尚不清楚。在这里，我们报告在 DSS 诱导的结肠炎期间，Arg1 敲除小鼠中 MDSC 的比例降低。Arg1 敲除小鼠的结肠中 IL-17A 水平降低但 IL-17F 水平显著增加，导致严重的组织损伤和高死亡率。雌激素受体 (ESR) 的激活增加了 MDSC 中的 pSTAT3 水平，进而导致 MDSC 中 Arg-1 和诱导型一氧化氮合酶的表达增加。增加的 IL-17A 水平和降低的 IL-17F 水平减轻了随后小鼠的结肠炎。总之，这些发现表明在 MDSC 中 ESR/STAT3 信号激活后，MDSC 衍生的 Arg-1 在结肠炎中发挥保护作用。高水平的 Arg-1 有利于在小鼠的结肠中积累更多的 IL-17A，但降低 IL-17F 的表达，最终导致结肠炎的缓解，这表明 MDSC 衍生的 Arg-1 对控制炎症性肠病具有潜在的临床影响。
