Effects of a low-dose IL-2 treatment in HLA-B27 transgenic rat model of spondyloarthritis.
Effects of a low-dose IL-2 treatment in HLA-B27 transgenic rat model of spondyloarthritis.
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DOI：
10.1186/s13075-021-02559-y
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发表时间：
2021-07-16
影响因子：
4.9
通讯作者：
Breban M
中科院分区：
文献类型：
--
作者：
Araujo LM;Jouhault Q;Fert I;Bouiller I;Chiocchia G;Breban M
HLA-B27/人β2m转基因大鼠（b27 -大鼠）出现一种类似于脊椎关节炎（SpA）的炎症性疾病，通过调节性T细胞（Treg）产生IL-10/IL-17。Treg在控制致病性炎症过程中起重要作用。白细胞介素2 （IL-2）是一种促进Treg细胞存活和功能的细胞因子，因此可能具有治疗SpA的功效。在这里，我们在b27大鼠中使用低剂量的IL-2治疗来验证这一假设。4周龄的b27大鼠（发病前）和非转基因（NTG）窝鼠腹腔注射重组人IL-2（赛诺菲®，2,000IU/注射）或PBS，每周3天，持续6周。根据临床（体重、腹泻、关节炎）、组织学（结肠近端和远端、盲肠、回肠和跗骨/踝关节）评分以及脾脏和淋巴结（LN）中Treg的频率来评估治疗效果。IL-2给药对B27-或ntg -大鼠的体重增加没有影响。治疗6周后，il -2治疗组和对照组b27大鼠的临床疾病评分恶化相似。b27大鼠肠道和关节的宏观和组织学评价显示明显的炎症；然而，没有观察到与IL-2治疗相关的变化。在b27大鼠中，IL-2处理后脾脏中Treg的百分比适度增加，但在这些大鼠的肠系膜和外周LN中没有。我们的数据表明，疾病发作前给予低剂量的IL-2对提高Treg有中等效果，但不能阻止b27大鼠的SpA发展。在线版本包含补充材料，可在10.1186/s13075-021-02559-y获得。
HLA-B27/human β2m transgenic rats (B27-rats) develop an inflammatory disorder resembling spondyloarthritis (SpA) with dysregulated IL-10/IL-17 production by regulatory T cells (Treg). Treg plays a major role in controlling pathogenic inflammatory processes. Interleukin 2 (IL-2), a cytokine which promotes Treg cell survival and function, may thus have therapeutic efficacy in SpA. Here, we tested this hypothesis using a low dose of IL-2 treatment in B27-rat. B27-rats aged 4 weeks (before disease onset) and nontransgenic (NTG) littermates were administered intraperitoneally recombinant human IL-2 (Sanofi®; 2,000IU/injection) or PBS, 3 days per week during 6 weeks. Assessment of treatment effect was performed, based on clinical (weight, diarrhea, arthritis), histological (proximal and distal colon, caecum, ileum and tarsal/ankle joint) scores, and frequency of Treg in the spleen and lymph nodes (LN). IL-2 administration had no effect on weight gain, either in B27- or NTG-rats. Over the 6 weeks of treatment, the clinical disease score worsened similarly in both IL-2-treated and control groups of B27-rats. The macroscopic and histological evaluation of gut and joints showed marked inflammation in B27-rats; however, no change related to IL-2 treatment was observed. In the B27-rats, the percentage of Treg was moderately increased after IL-2 treatment in the spleen, but neither in mesenteric nor peripheral LN in those rats. Our data demonstrate that a low dose of IL-2 administered before disease onset was moderately effective for boosting Treg but failed to prevent SpA development in B27-rat. The online version contains supplementary material available at 10.1186/s13075-021-02559-y.
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影响因子：
27.4
作者：
Rosenzwajg, Michelle;Lorenzon, Roberta;Klatzmann, David
通讯作者：
Klatzmann, David
DOI：
10.1002/iid3.364
发表时间：
2020-12
期刊：
Immunity, inflammation and disease
影响因子：
--
作者：
Sun H;Zhao Y;Wang K;Zhu L;Dong J;Zhao J;Wang Y;Li H;Sun X;Lu Y
通讯作者：
Lu Y
影响因子：
4.6
作者：
Guo H;Zheng M;Zhang K;Yang F;Zhang X;Han Q;Chen ZN;Zhu P
通讯作者：
Zhu P
影响因子：
--
作者：
Glatigny, Simon;Fert, Ingrid;Breban, Maxime
通讯作者：
Breban, Maxime
影响因子：
44.5
作者：
Hartemann, Agnes;Bensimon, Gilbert;Klatzmann, David
通讯作者：
Klatzmann, David