Effects of rIL2/anti-IL2 antibody complex on chikungunya virus-induced chronic arthritis in a mouse model.
Effects of rIL2/anti-IL2 antibody complex on chikungunya virus-induced chronic arthritis in a mouse model.
复制标题
DOI：
10.1038/s41598-023-34578-x
复制
发表时间：
2023-05-05
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
基孔肯雅病毒（CHIKV）的特点是致残性关节疼痛，可导致约四分之一的患者持续性关节炎。目前，没有标准治疗可用于慢性CHIKV关节炎。我们的初步数据表明，白细胞介素-2（IL-2）水平和调节性T细胞（Treg）功能的降低可能在CHIKV关节炎发病机制中发挥作用。用于自身免疫性疾病的基于低剂量IL 2的疗法已显示上调Tcl 3，并且将IL 2与抗IL 2抗体复合可延长IL 2的半衰期。使用CHIKV后关节炎的小鼠模型来测试重组IL 2（rIL 2）、抗IL 2单克隆抗体（mAb）和复合物对跗关节炎症、外周IL 2水平、TcR、CD 4+效应T细胞（Teff）和组织学疾病评分的影响。复合治疗导致最高水平的IL 2和Teffs，但也增加了Teffs，因此没有显著降低炎症或疾病评分。然而，具有适度增加的IL 2和活化的Tcl 3水平的抗体组导致平均疾病评分降低。这些结果表明，rIL 2/抗IL 2复合物刺激CHIKV后关节炎中的Teffs和Teffs，而抗IL 2 mAb增加IL 2可用性足以使免疫环境向致耐受性环境转变。
Chikungunya virus (CHIKV) is characterized by disabling joint pain that can cause persistent arthritis in approximately one-fourth of patients. Currently, no standard treatments are available for chronic CHIKV arthritis. Our preliminary data suggest that decreases in interleukin-2 (IL2) levels and regulatory T cell (Treg) function may play a role in CHIKV arthritis pathogenesis. Low-dose IL2-based therapies for autoimmune diseases have been shown to up-regulate Tregs, and complexing IL2 with anti-IL2 antibodies can prolong the half-life of IL2. A mouse model for post-CHIKV arthritis was used to test the effects of recombinant IL2 (rIL2), an anti-IL2 monoclonal antibody (mAb), and the complex on tarsal joint inflammation, peripheral IL2 levels, Tregs, CD4 + effector T cells (Teff), and histological disease scoring. The complex treatment resulted in the highest levels of IL2 and Tregs, but also increased Teffs, and therefore did not significantly reduce inflammation or disease scores. However, the antibody group, which had moderately increased levels of IL2 and activated Tregs, resulted in a decreased average disease score. These results suggest the rIL2/anti-IL2 complex stimulates both Tregs and Teffs in post-CHIKV arthritis, while the anti-IL2 mAb increases IL2 availability enough to shift the immune environment towards a tolerogenic one.
登录
查看更多内容
影响因子：
27.4
作者：
Rosenzwajg, Michelle;Lorenzon, Roberta;Klatzmann, David
通讯作者：
Klatzmann, David
DOI：
10.3390/diseases6040095
发表时间：
2018-10-20
期刊：
Diseases (Basel, Switzerland)
影响因子：
--
作者：
Chang, Aileen Y;Tritsch, Sarah;Bethony, Jeff M
通讯作者：
Bethony, Jeff M
DOI：
10.1073/pnas.0909384107
发表时间：
2010-02-02
影响因子：
11.1
作者：
Letourneau, Sven;van Leeuwen, Ester M. M.;Boyman, Onur
通讯作者：
Boyman, Onur
影响因子：
5.4
作者：
Lee WW;Teo TH;Her Z;Lum FM;Kam YW;Haase D;Rénia L;Rötzschke O;Ng LF
通讯作者：
Ng LF
影响因子：
32.4
作者：
Yamaguchi, Tomoyuki;Hirota, Keiji;Sakaguchi, Shimon
通讯作者：
Sakaguchi, Shimon