Division of Surgical Research, Department of Surgery, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island.
Division of Surgical Research, Department of Surgery, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island; Division of Trauma and Surgical Critical Care, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island.
Am J Pathol. 2018 Sep;188(9):2097-2108. doi: 10.1016/j.ajpath.2018.05.009. Epub 2018 Jun 20.
Sepsis remains a major public health concern, characterized by marked immune dysfunction. Innate lymphoid cells develop from a common lymphoid precursor but have a role in orchestrating inflammation during innate response to infection. Here, we investigate the pathologic contribution of the group 2 innate lymphoid cells (ILC2s) in a murine model of acute septic shock (cecal ligation and puncture). Flow cytometric data revealed that ILC2s increase in number and percentage in the small intestine and in the peritoneal cells and inversely decline in the liver at 24 hours after septic insult. Sepsis also resulted in changes in ILC2 effector cytokine (IL-13) and activating cytokine (IL-33) in the plasma of mice and human patients in septic shock. Of interest, the sepsis-induced changes in cytokines were abrogated in mice deficient in functionally invariant natural killer T cells. Mice deficient in IL-13-producing cells, including ILC2s, had a survival advantage after sepsis along with decreased morphologic evidence of tissue injury and reduced IL-10 levels in the peritoneal fluid. Administration of a suppressor of tumorigenicity 2 (IL-33R) receptor-blocking antibody led to a transient survival advantage. Taken together, these findings suggest that ILC2s may play an unappreciated role in mediating the inflammatory response in both mice and humans; further, modulating ILC2 response in vivo may allow development of immunomodulatory strategies directed against sepsis.
败血症仍然是一个主要的公共卫生关注点，其特征是明显的免疫功能障碍。先天淋巴细胞从共同的淋巴前体发育而来，但在感染时固有免疫反应中起协调炎症的作用。在这里，我们研究了在急性败血性休克（盲肠结扎和穿孔）的小鼠模型中，第 2 组先天淋巴细胞（ILC2）的病理贡献。流式细胞术数据显示，在败血症损伤后 24 小时，ILC2 在小肠和腹膜细胞中的数量和百分比增加，而在肝脏中则减少。败血症还导致感染性休克小鼠和人类患者血浆中 ILC2 效应细胞因子（IL-13）和激活细胞因子（IL-33）的变化。有趣的是，在功能不变的自然杀伤 T 细胞缺陷小鼠中，败血症引起的细胞因子变化被消除。缺乏产生 IL-13 的细胞（包括 ILC2）的小鼠在败血症后具有生存优势，同时组织损伤的形态学证据减少，腹膜液中的 IL-10 水平降低。施用肿瘤抑制因子 2（IL-33R）受体阻断抗体导致短暂的生存优势。总之，这些发现表明 ILC2 可能在介导小鼠和人类的炎症反应中发挥了未被认识的作用；此外，在体内调节 ILC2 反应可能允许针对败血症开发免疫调节策略。
