白细胞介素-22 通过诱导抑制性 F4/80Ly6GLy6C 细胞群来保护内毒素血症。

Interleukin-22 protects from endotoxemia by inducing suppressive F4/80Ly6GLy6C cells population.

机构信息

Central Laboratory, Department of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, 528 Zhangheng Road, Shanghai, 201203, China.

Department of Emergency Internal Medicine, Shuguang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China.

出版信息

BMC Immunol. 2022 Sep 19;23(1):45. doi: 10.1186/s12865-022-00511-6.

DOI:10.1186/s12865-022-00511-6

PMID:36123595

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9484229/

Abstract

BACKGROUND

Excessive inflammatory response is the primary cause of early death in patients with endotoxemia. Interleukin 22 (IL-22) has been shown to play critical roles in the modulation of infectious diseases, but its function in regulating immune responses during endotoxemia remains unclear.

METHODS

Lipopolysaccharide (LPS) was used to induce endotoxemia mouse model with or without a recombinant fusion protein containing human IL-22 (F-652). IL-6, TNF-α, IL-1β, and MCP-1 were measured by ELISA assays. The type of macrophage was assessed by flow cytometry. Real-time PCR was used to detect the expression of S100A9.

RESULTS

We found that F-652 injection significantly improved the survival rates and reduced pro-inflammatory cytokines (IL-6, TNF-a, IL-1β, MCP-1) in LPS-induced endotoxemia mice. However, the mice injected with F-652 had a higher number of infiltrated immune cells after LPS treatment, suggesting an impaired immune response. Flow cytometry analysis showed a higher number of F4/80Ly6GLy6C cells that highly expressed M2-like macrophage markers (Ym1, Arg, CCL17) in the peritoneal cavity of the F-652-treated endotoxemia mice. Further investigation found that these suppressive M2 macrophages might be induced by F-652 since the F-652 treatment could increase S100A9 in vitro.

CONCLUSIONS

Our study suggests that IL-22 has a protective role against endotoxemia by inducing the development of immunosuppressive cells through S100A9.

摘要

背景

过度的炎症反应是内毒素血症患者早期死亡的主要原因。白细胞介素 22（IL-22）已被证明在调节感染性疾病方面发挥着关键作用，但它在调节内毒素血症期间的免疫反应中的功能仍不清楚。

方法

使用脂多糖（LPS）诱导内毒素血症小鼠模型，并用含有人白细胞介素 22（F-652）的重组融合蛋白进行处理。通过 ELISA 测定试剂盒测定 IL-6、TNF-α、IL-1β 和 MCP-1 的水平。通过流式细胞术评估巨噬细胞的类型。实时 PCR 用于检测 S100A9 的表达。

结果

我们发现，F-652 注射显著提高了 LPS 诱导的内毒素血症小鼠的存活率，并降低了促炎细胞因子（IL-6、TNF-a、IL-1β、MCP-1）的水平。然而，与 LPS 处理后的野生型小鼠相比，F-652 处理的 LPS 诱导的内毒素血症小鼠中浸润的免疫细胞数量更高，表明免疫反应受损。流式细胞术分析显示，F-652 处理的内毒素血症小鼠腹腔中表达 M2 样巨噬细胞标志物（Ym1、Arg、CCL17）的 F4/80Ly6GLy6C 细胞数量更多。进一步的研究发现，这些抑制性 M2 巨噬细胞可能是由 F-652 诱导的，因为 F-652 处理可以在体外增加 S100A9 的表达。