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Anti-Arthritic Activity of Schistosoma mansoni and Trichinella spiralis Derived-Antigens in Adjuvant Arthritis in Rats: Role of FOXP3+ Treg Cells

机译:曼氏血吸虫和旋毛虫旋毛虫抗原的抗关节炎活性在大鼠佐剂性关节炎中:FOXP3 + Treg细胞的作用

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摘要

A growing body of evidence supports the concept of helminths therapy in a variety of autoimmune diseases. Here, we aimed to investigate the protective effects of autoclaved Schistosoma mansoni antigen (ASMA) and Trichinella spiralis antigen (ATSA) on the clinical and immunopathological features of rheumatoid arthritis (RA). Adjuvant arthritis was induced by subcutaneous and intradermal injections of complete Freund’s adjuvant into the plantar surface of the right hind paw and the root of the tail, respectively. Rats were randomly assigned to serve as normal control, untreated arthritis, ASMA or ATSA-treated arthritis groups. Antigens were given by intradermal injection in two doses, two weeks apart. The development, progression of arthritic features, and the impact on animals’ gait and body weight were followed up for 4 weeks. The associated changes in serum cytokines (IL-17, IFN-γ and IL-10), joints’ histopathology and immunohistochemistry of Foxp3+ T regulatory cells (Tregs) were evaluated at the end of the study. Treatment with either ASMA or ATSA attenuated the progression of clinical features of polyarthritis, improved gait and body weight gain, reduced the elevated serum IL-17 and further increased both IFN-γ and IL-10. Histopathologically, this was associated with a remarkable regression of paws’ inflammation that was limited only to the subcutaneous tissue, and a significant increase in the number of Foxp 3+ cells versus the untreated arthritis group. In conclusion, both Schistosoma mansoni and Trichinella spiralis derived antigens exerted protective effect against adjuvant arthritis with better effect achieved by ASMA treatment. This anti-arthritic activity is attributed to upregulation of the Foxp3+ Tregs, with subsequent favorable modulation of both pro- and anti-inflammatory cytokines. The use of autoclaved parasitic antigens excludes the deleterious effects of imposing helminthic infection by using live parasites, which may pave the way to a new therapeutic modality in treating RA.
机译:越来越多的证据支持在各种自身免疫性疾病中使用蠕虫疗法的概念。在这里,我们旨在研究高压灭菌的曼氏血吸虫抗原(ASMA)和旋毛虫旋毛虫抗原(ATSA)对类风湿关节炎(RA)的临床和免疫病理特征的保护作用。皮下和皮内注射弗氏完全佐剂分别诱发右后爪的足底表面和尾巴的根部,从而诱发佐剂性关节炎。将大鼠随机分为正常对照组,未治疗的关节炎,ASMA或ATSA治疗的关节炎组。两次皮内注射,间隔两周给予抗原。随访了4周的关节炎特征的发展,进展以及对动物步态和体重的影响。在研究结束时,评估了血清中的细胞因子(IL-17,IFN-γ和IL-10),Foxp3 + T调节细胞(Tregs)的关节组织病理学和免疫组织化学的相关变化。用ASMA或ATSA进行治疗可减轻多关节炎的临床特征,改善步态和体重,降低血清IL-17升高,并进一步增加IFN-γ和IL-10。从组织病理学上讲,这与只限于皮下组织的爪子炎症显着消退有关,并且与未经治疗的关节炎组相比,Foxp 3+细胞的数量显着增加。总之,曼氏血吸虫和旋毛虫旋毛虫抗原均对佐剂性关节炎具有保护作用,而通过ASMA治疗可获得更好的效果。这种抗关节炎活性归因于Foxp3 + Tregs的上调,随后对促炎和消炎细胞因子均进行了有利的调节。高压灭菌的寄生虫抗原的使用排除了通过使用活寄生虫施加蠕虫感染的有害影响,这可能为治疗RA的新治疗方式铺平了道路。

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