Department of Rheumatology and Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Rheumatology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
J Immunol Res. 2023 Oct 5;2023:2689360. doi: 10.1155/2023/2689360. eCollection 2023.
Macrophage activation syndrome (MAS) is a fatal inflammatory condition, which is often associated with the elevation of multiple proinflammatory cytokines and multiple organ dysfunction. Previous studies have shown that ST2 contributes to T cell overactivation and plays a detrimental role in mouse models of primary hemophagocytic lymphohistiocytosis. The purpose of this study was to investigate the role of the IL-33/ST2 axis in a mouse model of MAS induced by repeated injections of cytosine-phosphate-guanine (CpG).
Serum cytokines were determined using the cytometric bead array by flow cytometry. IL-33 and ST2 were detected by immunohistochemistry and real-time quantitative PCR in the liver and spleen of mice. CD3 and F4/80 in the liver were detected by immunohistochemistry. Inflammatory macrophages and effector memory T lymphocytes were detected by flow cytometry.
The CpG-induced MAS model was successfully induced after repeated CpG injections, presenting with hypercytokinemia and hepatosplenomegaly. The numbers of IL-33 positive cells in the liver and spleen decreased significantly, while the expression of ST2 in the liver tended to increase in the mice with MAS. and knockout mice showed similar levels of hepatosplenomegaly, peripheral blood count, and cytokine storm when compared with wild-type (WT) mice after induction of MAS. There were also no significant differences in liver pathology (including inflammatory cell infiltration of CD3 and F4/80) and levels of splenic inflammatory macrophages and effector memory T cells between the WT and knockout mice.
These results suggested that IL-33 decreased in the liver and spleen tissues of MAS mice. Further results suggest that and knockout mice have no treatment potential in CpG-induced MAS. Thus, the IL-33/ST2 axis has little effect on the prognosis of CpG-induced MAS.
巨噬细胞活化综合征（MAS）是一种致命的炎症性疾病，常伴有多种促炎细胞因子的升高和多器官功能障碍。先前的研究表明，ST2 有助于 T 细胞过度激活，并在原发性噬血细胞性淋巴组织细胞增多症的小鼠模型中发挥有害作用。本研究旨在探讨白细胞介素-33（IL-33）/ST2 轴在反复注射胞嘧啶-磷酸-鸟嘌呤（CpG）诱导的 MAS 小鼠模型中的作用。
通过流式细胞术的细胞因子流式微球阵列分析测定血清细胞因子。采用免疫组织化学和实时定量 PCR 检测肝脾中 IL-33 和 ST2 的表达。采用免疫组织化学检测肝 CD3 和 F4/80。采用流式细胞术检测炎症性巨噬细胞和效应记忆 T 淋巴细胞。
CpG 重复注射成功诱导 MAS 模型，表现为高细胞因子血症和肝脾肿大。MAS 小鼠肝脾中 IL-33 阳性细胞数量明显减少，而肝 ST2 表达趋于增加。与野生型（WT）小鼠相比，和 基因敲除（KO）小鼠在诱导 MAS 后肝脾肿大、外周血计数和细胞因子风暴程度相似。WT 和 KO 小鼠肝组织病理学（包括 CD3 和 F4/80 炎性细胞浸润）和脾炎症性巨噬细胞及效应记忆 T 细胞水平无明显差异。
这些结果表明 MAS 小鼠肝脾组织中 IL-33 减少。进一步的结果表明，和 KO 小鼠在 CpG 诱导的 MAS 中没有治疗潜力。因此，IL-33/ST2 轴对 CpG 诱导的 MAS 预后影响不大。
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