背景：

       狼疮肾炎(Lupus nephritis, LN)是系统性红斑狼疮(systemic lupus erythematosus, SLE)最常见且对预后影响较大的脏器损伤之一。研究表明MRL/lpr狼疮模型小鼠肾脏组织中存在IL-22富集，且与肾脏病变程度相关。LN患者外周血及肾脏组织中产IL-22的Th22细胞比例升高，提示IL-22/Th22可能参与LN发生发展。已知pDC可促进Th22分化，且pDC作为分泌I型干扰素(type I interferon, IFN-Ⅰ)的主要细胞参与SLE发病机制。

方法：

       通过293T报告细胞系和LEGENDplex两种检测方法测定SLE患者血清IFN-I水平，并通过流式细胞仪检测体外细胞孵育实验后Th22细胞分化情况，以探讨不同浓度IFN-I对Th22细胞分化产生的影响。对LN患者肾脏组织进行免疫组化(Immunohistochemistry, IHC)染色并观察IL-22/IL-22R1表达情况。在NZB/W F1小鼠中初步检测其狼疮肾炎发病前后肾脏组织IL-22/IL-22R1表达情况，以帮助了解IFN-I/IL-22轴在LN免疫病理中的作用机制。

结果：

       SLE患者血清中IFN-I水平显著高于健康对照(Healthy control, HC)组(p=0.0863)。与以皮肤受累为主要表现的系统性红斑狼疮(cutaneous lupus erythematosus, LC)患者相比，LN患者血清中IL-22水平差异不大(p=0.908)。流式细胞术和实时定量聚合酶链式反应(real-time quantitative polymerase chain reaction, RT-qPCR)结果显示高浓度IFN-α2b可抑制Th22细胞分化和IL-22 mRNA基因表达。对肾脏组织进行IL-22/IL-22R1免疫组化染色及定量分析发现，LN组IL-22/IL-22R1水平高于HC组。在NZB/W F1小鼠发病后(28周龄)的肾脏组织IL-22/IL-22R1 表达高于发病前(8周龄) (p=0.154, 0.015 & 0.0157)。

结论：

       IL-22/Th22可能参与LN的发生发展，IFN-I可能在IL-22/Th22通路激活中发挥一定作用。IFN-I 活性与血清IL-22含量间存在负相关。IFN-I通路相关治疗方案获益情况需进一步实验论证。

Backgrounds：

       Lupus nephritis (LN) is one of the most common organ injuries of systemic lupus erythematosus (SLE) and has great influence on prognosis of patients. The results showed that IL-22 is enriched in the kidney tissue of MRL/lpr lupus model mice, which is related to the degree of kidney lesions. The proportion of Th22 cells containing IL-22 in peripheral blood and kidney tissue of LN patients increased, suggesting that IL-22/Th22 may be involved in the development of LN. It has been known that pDC could promote Th22 differentiation, and pDC is involved in the pathogenesis of SLE as the main cell secreting type I interferon (IFN-Ⅰ).

Methods：

       The serum IFN-I levels of SLE patients were measured by 293T reporter cell line and LEGENDplex detection methods, and Th22 cell differentiation was measured by flow cytometry after incubation experiment in vitro, so as to explore the effects of different concentrations of IFN-I on Th22 cell differentiation. Immunohistochemistry (IHC) staining of kidney tissues from LN patients was performed while IL-22/IL-22R1 expression was observed. The expression of IL-22/IL-22R1 in the kidney tissues of NZB/W F1 mice before and after the onset of lupus nephritis was preliminarily detected to help understand the mechanism of action of the IFN-I/IL-22 in the immunopathology of LN.

Results：

       The serum IFN-I level in SLE patients was significantly higher than that in Healthy control (HC) group (p=0.0863). Compared with patients with systemic lupus erythematosus (LC) mainly manifested by skin involvement, there was no significant difference in the serum levels of IL-22 in LN patients (p=0.908). Flow cytometry and real-time quantitative polymerase chain reaction (RT-qPCR) showed that high concentration of IFN-α2b inhibited Th22 cell differentiation and IL-22 mRNA gene expression. Immunohistochemical staining and quantitative analysis of IL-22/IL-22R1 in kidney tissues showed that the level of IL-22/IL-22R1 in LN group was higher than that in HC group. The expression of IL-22/IL-22R1 in kidney tissue of NZB/W F1 mice after onset (28 weeks of age) was higher than that before onset (8 weeks of age) (p=0.154, 0.015 & 0.0157).

Conclusions：

       There was a negative correlation between IFN-I activity and serum IL-22 content. IL-22/Th22 may be involved in the development of LN, and IFN-I may play a role in the activation of IL-22/Th22 pathway. Further experiments are needed to demonstrate the benefits of IFN-I pathways.