Background: CXCL4 plays an essential role in the regulation of multiple immune diseases. However, the underlying role of CXCL4 is still not clear in sepsis. Aim: In the present study, we aimed to investigate the function of CXCL4 in sepsis.

Methods: Sepsis model was constructed on mouse. Flow cytometry was used to determine the ratio of CD4⁺CD25⁺FOXP3⁺Treg cells. ELISA assays were used to determine the levels of CXCL4, IL-6, IL-10, and TNF-α respectively. Western blot was used to examine protein contents.

Results: Our results suggested that the serum level of CXCL4 was upregulated in patients with sepsis and positively associated with the ratio of human CD4⁺CD25⁺FOXP3⁺Treg cells. To further examine the role of CXCL4 in sepsis, we constructed the mouse sepsis model. Our results indicated that the mouse antibody of CXCL4 treatment reduced the expression of urine creatinine and urea nitrogen in sepsis model. Moreover, the frequency of CD25⁺FOXP3⁺ mouse regulatory T cells (Tregs) cells was decreased in mouse CD4⁺ T cells in the presence of mouse CXCL4 antibody. Further, the mouse recombinant protein CXCL4 was used to culture normal mouse CD4⁺ T cells in vitro. Our finding indicated that the recombinant protein CXCL4 promoted the percentage of mouse CD25⁺FOXP3⁺Treg cells and enhanced the phosphorylation of STAT5 in mouse CD4⁺ T cells in a dose-dependent manner. However, these effects were significantly reversed by the STAT5 inhibitor (p < .001). Conclusion: our findings not only indicated the function and signalling pathway of CXCL4 in CD4⁺ T cells but also provided novel insight and target in sepsis treatment.

背景： CXCL4在多种免疫疾病的调节中起着至关重要的作用。但是，CXCL4的潜在作用在败血症中仍然不清楚。目的：在本研究中，我们旨在研究CXCL4在脓毒症中的功能。

方法：在小鼠上建立脓毒症模型。流式细胞仪用于确定CD4 ⁺ CD25 ⁺ FOXP3 ⁺ Treg细胞的比例。ELISA分析用于分别确定CXCL4，IL-6，IL-10和TNF-α的水平。使用蛋白质印迹法检查蛋白质含量。

结果：我们的结果表明，脓毒症患者的血清CXCL4水平上调，并且与人CD4 ⁺ CD25 ⁺ FOXP3 ⁺ Treg细胞的比例呈正相关。为了进一步检查CXCL4在败血症中的作用，我们构建了小鼠败血症模型。我们的结果表明，在脓毒症模型中，CXCL4处理的小鼠抗体降低了尿肌酐和尿素氮的表达。此外，在存在小鼠CXCL4抗体的情况下，小鼠CD4 ⁺ T细胞中CD25 ⁺ FOXP3 ⁺小鼠调节性T细胞（Tregs）的频率降低。此外，小鼠重组蛋白CXCL4用于培养正常小鼠CD4 ⁺体外T细胞。我们的发现表明重组蛋白CXCL4以剂量依赖的方式促进了小鼠CD25 ⁺ FOXP3 ⁺ Treg细胞的百分比并增强了STAT5在小鼠CD4 ⁺ T细胞中的磷酸化。但是，这些作用被STAT5抑制剂显着逆转（p  <.001）。结论：我们的发现不仅表明CXCL4在CD4 ⁺ T细胞中的功能和信号通路，而且为脓毒症治疗提供了新的见识和靶标。