National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, China; Core Research Laboratory, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, China.
National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, China.
Int J Biochem Cell Biol. 2021 Jul;136:105970. doi: 10.1016/j.biocel.2021.105970. Epub 2021 Mar 24.
The role of the spleen in sepsis is still controversial. Therefore, we investigated the effect of the spleen on sepsis-induced immune dysfunction in C57BL/6 mice subjected to caecal ligation and puncture (CLP). Changes in different immune cells and apoptotic cells in the spleen and peripheral blood were observed 4, 24 and 48 h after CLP. Then, we determined that 48 h following CLP was the most significant period of immunosuppression. Next, we divided the mice into four groups: control, CLP, CLP + spx (splenectomy 48 h after CLP) and spx + CLP (splenectomy surgery two weeks before CLP). Compared with the CLP mice, the CLP + spx and spx + CLP mice had improved survival rates and organ injuries, increased expression of inflammatory factors, a decreased proportion of regulatory T cells (Tregs), and reduced expression of the genes involved in the programmed cell death 1 and its ligand 1 (PD1-PDL1) pathway in immune cells and T-cell immunoglobulin-mucin domain 3 (Tim 3) and Galectin9 in the liver and lungs after 72 h in late-phase sepsis. In addition, the expression of PD-1 was significantly reduced in T cells in spx + CLP mice, and the expression of PD-L1 in myeloid-derived suppressor cells (MDSCs) was reduced in the CLP + spx group, especially in macrophages. These findings suggested that splenectomy could protect septic mice from exhaustion of immune cells by reducing the proliferation of Treg cells and expression of the PD-1/PD-L1 axis in immune cells during the immunosuppressive stage of sepsis. Splenectomy could also reduce liver and lung injuries possibly via the Tim 3 and/or Galectin-9 axis. The spleen is an important regulator of the occurrence and development of sepsis, which provides a new perspective to improve the prognosis of sepsis by regulating the spleen.
脾脏在脓毒症中的作用仍存在争议。因此，我们研究了脾脏在盲肠结扎穿孔（CLP）后 C57BL/6 小鼠脓毒症诱导免疫功能障碍中的作用。在 CLP 后 4、24 和 48 小时观察脾脏和外周血中不同免疫细胞和凋亡细胞的变化。然后，我们确定 CLP 后 48 小时是免疫抑制最显著的时期。接下来，我们将小鼠分为四组：对照组、CLP 组、CLP+spx（CLP 后 48 小时脾切除术）和 spx+CLP（CLP 前两周脾切除术）。与 CLP 组相比，CLP+spx 和 spx+CLP 组的生存率和器官损伤得到改善，炎症因子表达增加，调节性 T 细胞（Tregs）比例降低，程序性细胞死亡 1 及其配体 1（PD1-PDL1）通路相关基因在免疫细胞和 T 细胞免疫球蛋白粘蛋白结构域 3（Tim 3）和 Galectin9 在晚期脓毒症 72 小时后的肝脏和肺部表达减少。此外，在 spx+CLP 小鼠中 T 细胞的 PD-1 表达显著降低，在 CLP+spx 组中髓源抑制细胞（MDSCs）的 PD-L1 表达降低，尤其是巨噬细胞。这些发现表明，脾切除术通过减少 Treg 细胞的增殖和脓毒症免疫抑制阶段免疫细胞中 PD-1/PD-L1 轴的表达，可保护脓毒症小鼠免受免疫细胞衰竭。脾切除术还可能通过 Tim 3 和/或 Galectin-9 轴减轻肝和肺损伤。脾脏是脓毒症发生发展的重要调节者，为通过调节脾脏改善脓毒症预后提供了新视角。
