Department of Dermatology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Department of Dermatology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.
Lupus. 2020 Mar;29(3):290-302. doi: 10.1177/0961203320903802. Epub 2020 Feb 10.
The immune system is one of the most complex regulatory systems in the body and is essential for the maintenance of homeostasis. Despite recent breakthroughs in immunology, the regulation of the immune system and the etiology of autoimmune diseases such as lupus remain unclear. Systemic lupus erythematosus is a systemic autoimmune disease with abnormally and inconsistently expressed pro-inflammatory cytokines. Pyroptosis is a pro-inflammatory form of programmed cell death that is associated with systemic lupus erythematosus. The thymus and spleen are important immune organs involved in systemic lupus erythematosus. Therefore, this study investigated the difference in expression of pyroptosis-inducing pro-inflammatory cytokines between the spleen and thymus in lupus model mice and in control mice, to describe immune regulation at the organ level.
To investigate differences in the expression of pyroptosis-inducing cytokines in the spleen and thymus and to explore immune regulatory networks at the organ level.
Two groups of lupus mice and two groups of control mice were utilized for this study. Using the thymus and spleen of experimental animals, mRNA expression levels of five pyroptosis-inducing cytokines (interleukin 1β, interleukin 18, NLRP3, caspase-1 and TNF-α) were determined via quantitative polymerase chain reaction. In addition, tissue distribution of these cytokines was investigated via immunohistochemistry.
All five pyroptosis-inducing inflammatory cytokines showed higher expression in the spleen than in the thymus ( < 0.05). Moreover, the spleen/thymus expression ratios of all five pyroptosis-inducing cytokines were not statistically different between the four experimental groups. Expression of all five cytokines exhibited a stable ratio (spleen/thymus ratios). This distinctive stable spleen/thymus ratio was consistent in all four experimental groups. The stable spleen/thymus ratios of the five inflammatory cytokines were as follows: interleukin 1β (2.02 ± 0.9), interleukin 18 (2.07 ± 1.06), caspase-1 (1.93 ± 0.66), NLRP3 (3.14 ± 1.61) and TNF-α (3.16 ± 1.36). Immunohistochemical analysis showed the cytokines were mainly expressed in the red pulp region of the spleen and the medullary region of the thymus, where immune-activated cells aggregated.
The stable spleen/thymus expression ratios of pyroptosis-inducing cytokines indicated that immune organs exhibit strictly regulated functions to maintain immune homeostasis and adapt to the environment.
免疫系统是人体中最复杂的调节系统之一，对于维持内环境稳定至关重要。尽管免疫学领域最近取得了突破，但免疫系统的调节以及狼疮等自身免疫性疾病的病因仍不清楚。系统性红斑狼疮是一种系统性自身免疫性疾病，其促炎细胞因子表达异常且不一致。细胞焦亡是一种与系统性红斑狼疮相关的促炎形式的程序性细胞死亡。胸腺和脾脏是参与系统性红斑狼疮的重要免疫器官。因此，本研究旨在探讨狼疮模型小鼠和对照小鼠脾脏和胸腺中诱导细胞焦亡的促炎细胞因子表达的差异，以描述器官水平的免疫调节。
探讨脾脏和胸腺中诱导细胞焦亡的细胞因子表达的差异，探索器官水平的免疫调节网络。
本研究使用了两组狼疮小鼠和两组对照小鼠。通过实验动物的胸腺和脾脏，采用实时定量聚合酶链反应检测五种诱导细胞焦亡的细胞因子（白细胞介素 1β、白细胞介素 18、NLRP3、半胱天冬酶-1 和 TNF-α）的 mRNA 表达水平。此外，还通过免疫组织化学法研究了这些细胞因子的组织分布。
所有五种诱导细胞焦亡的炎症细胞因子在脾脏中的表达均高于胸腺（<0.05）。此外，在这四个实验组中，所有五种诱导细胞焦亡的细胞因子的脾脏/胸腺表达比值均无统计学差异。所有五种细胞因子的表达均表现出稳定的比值（脾脏/胸腺比值）。这种独特的稳定脾脏/胸腺比值在所有四个实验组中都是一致的。五种炎症细胞因子的稳定脾脏/胸腺比值如下：白细胞介素 1β（2.02±0.9）、白细胞介素 18（2.07±1.06）、半胱天冬酶-1（1.93±0.66）、NLRP3（3.14±1.61）和 TNF-α（3.16±1.36）。免疫组织化学分析表明，这些细胞因子主要在脾脏的红髓区和胸腺的髓质区表达，免疫激活细胞在此聚集。
诱导细胞焦亡的细胞因子的稳定脾脏/胸腺表达比值表明，免疫器官具有严格调节的功能，以维持免疫内稳态并适应环境。
