Esam Khanfar, Katalin Olasz, Szonja Gál, Erzsébet Gajdócsi, Béla Kajtár, Tamás Kiss, Péter Balogh, Timea Berki, Ferenc Boldizsár
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Circulating Tregs and T-helper subset ratios in the spleen and inguinal lymph nodes (LNs) were also examined using flow cytometry. The onset of severe inflammatory response was significantly delayed in SPE1 and SPE2 groups compared to control mice at early stages of GIA, which was associated with increased circulating Tregs. After the third immunization, as disease progressed, the severity scores were robustly increased in all mice. Nevertheless, in splenectomized mice, we observed reduced joint deterioration and cartilage damage, more Th2 cells in LNs, and reduced levels of pro-inflammatory cytokines and autoantibodies in their sera. Mesenteric LN cells of splenectomized mice exhibited weaker response in vitro against the rhG1 antigen compared to control mice spleen. 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引用次数: 0
摘要
脾脏在先天性免疫和适应性免疫以及类风湿性关节炎(RA)等自身免疫性疾病中发挥作用。我们在小鼠模型中研究了脾切除对自身免疫性关节炎早期和中期的影响。为了诱导重组人 G1 诱导的关节炎(GIA),用 rhG1 抗原对 BALB/c 小鼠腹腔免疫三次,每次间隔 4 周。免疫开始后第7天(SPE1)或第35天(SPE2)切除小鼠脾脏,检测小鼠的临床严重程度、关节放射学和组织学变化、血清炎性细胞因子和自身抗体水平以及rhG1特异性免疫反应,并与保留脾脏的对照组小鼠进行比较。此外,还使用流式细胞术检测了脾脏和腹股沟淋巴结中的循环 Tregs 和 T 辅助亚群比率。与对照组相比,SPE1 和 SPE2 组小鼠在 GIA 早期严重炎症反应的发生明显延迟,这与循环 Tregs 的增加有关。第三次免疫后,随着病情的发展,所有小鼠的严重程度评分都显著增加。尽管如此,我们观察到切除脾脏的小鼠关节退化和软骨损伤减轻,淋巴结中 Th2 细胞增多,血清中促炎细胞因子和自身抗体水平降低。与对照组小鼠的脾脏相比,脾切除小鼠的肠系膜淋巴结细胞在体外对 rhG1 抗原的反应较弱。总之,在 GIA 的早期阶段切除脾脏可延缓炎症反应,对严重的破坏性关节炎的发生和发展具有保护作用。
Splenectomy at early stage of autoimmune arthritis delayed inflammatory response and reduced joint deterioration in mice.
The spleen plays a role in innate and adaptive immunity, and autoimmune diseases like rheumatoid arthritis (RA). We investigated the effect of splenectomy in early and moderate stages of autoimmune arthritis in a mouse model. To induce recombinant human G1-induced arthritis (GIA), BALB/c mice were immunized intraperitoneally three times in 4-week intervals with the rhG1 antigen. Mice were splenectomized on day 7 (SPE1) or day 35 (SPE2) after the initiation of immunization; tested for clinical severity, joint radiological and histological changes, serum levels of inflammatory cytokines and autoantibodies, and rhG1-specific immune responses; and compared to those in control mice with spleen left intact. Circulating Tregs and T-helper subset ratios in the spleen and inguinal lymph nodes (LNs) were also examined using flow cytometry. The onset of severe inflammatory response was significantly delayed in SPE1 and SPE2 groups compared to control mice at early stages of GIA, which was associated with increased circulating Tregs. After the third immunization, as disease progressed, the severity scores were robustly increased in all mice. Nevertheless, in splenectomized mice, we observed reduced joint deterioration and cartilage damage, more Th2 cells in LNs, and reduced levels of pro-inflammatory cytokines and autoantibodies in their sera. Mesenteric LN cells of splenectomized mice exhibited weaker response in vitro against the rhG1 antigen compared to control mice spleen. In conclusion, splenectomy in the early stages of GIA delayed the inflammatory response, suggesting a protective effect against the development and progression of severe destructive arthritis.
期刊介绍:
Clinical & Experimental Immunology (established in 1966) is an authoritative international journal publishing high-quality research studies in translational and clinical immunology that have the potential to transform our understanding of the immunopathology of human disease and/or change clinical practice.
The journal is focused on translational and clinical immunology and is among the foremost journals in this field, attracting high-quality papers from across the world. Translation is viewed as a process of applying ideas, insights and discoveries generated through scientific studies to the treatment, prevention or diagnosis of human disease. Clinical immunology has evolved as a field to encompass the application of state-of-the-art technologies such as next-generation sequencing, metagenomics and high-dimensional phenotyping to understand mechanisms that govern the outcomes of clinical trials.