T-cell costimulation blockade is effective in experimental digestive and lung tissue fibrosis.
T-cell costimulation blockade is effective in experimental digestive and lung tissue fibrosis.
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DOI：
10.1186/s13075-018-1694-9
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发表时间：
2018-08-29
影响因子：
4.9
通讯作者：
Avouac J
中科院分区：
文献类型：
--
作者：
Boleto G;Guignabert C;Pezet S;Cauvet A;Sadoine J;Tu L;Nicco C;Gobeaux C;Batteux F;Allanore Y;Avouac J
我们的目的是研究阿巴西普在消化系统受累、肺纤维化和相关肺动脉高压（PH）的临床前小鼠模型中的疗效，模拟系统性硬化症（SSc）中的内脏受累。已在慢性移植物抗宿主病（cGvHD）小鼠模型中评价了阿巴西普（阿巴西普1 mg/mL，持续6周），其特征在于肝和肠纤维化，并且在Fra-2小鼠模型中（lmg/mL或10 mg/mL，持续4周），其特征在于间质性肺病（ILD）和肺血管重塑导致PH。阿巴西普显著降低肝转氨酶水平并显著改善结肠炎症。在Fra-2模型中，阿巴西普减轻ILD，胸部显微计算机断层扫描（CT）肺密度、纤维化组织学评分和肺生化标志物显著降低。此外，阿巴西普通过改善血管重塑和相关的心脏血流动力学损伤来逆转Fra-2小鼠的PH。阿巴西普显著降低Fra-2小鼠病变肺中的纤维化标志物水平、T细胞增殖和M1/M2巨噬细胞浸润。阿巴西普改善消化系统的参与，防止肺纤维化，并减弱PH。这些研究结果表明，阿巴西普可能是一个有吸引力的治疗方法超越皮肤纤维化的器官参与SSc。本文的在线版本（10.1186/s13075-018-1694-9）包含补充材料，可供授权用户使用。
We aimed to investigate the efficacy of abatacept in preclinical mouse models of digestive involvement, pulmonary fibrosis, and related pulmonary hypertension (PH), mimicking internal organ involvement in systemic sclerosis (SSc). Abatacept has been evaluated in the chronic graft-versus-host disease (cGvHD) mouse model (abatacept 1 mg/mL for 6 weeks), characterized by liver and intestinal fibrosis and in the Fra-2 mouse model (1 mg/mL or 10 mg/mL for 4 weeks), characterized by interstitial lung disease (ILD) and pulmonary vascular remodeling leading to PH. In the cGvHD model, abatacept significantly decreased liver transaminase levels and markedly improved colon inflammation. In the Fra-2 model, abatacept alleviated ILD, with a significant reduction in lung density on chest microcomputed tomography (CT), fibrosis histological score, and lung biochemical markers. Moreover, abatacept reversed PH in Fra-2 mice by improving vessel remodeling and related cardiac hemodynamic impairment. Abatacept significantly reduced fibrogenic marker levels, T-cell proliferation, and M1/M2 macrophage infiltration in lesional lungs of Fra-2 mice. Abatacept improves digestive involvement, prevents lung fibrosis, and attenuates PH. These findings suggest that abatacept might be an appealing therapeutic approach beyond skin fibrosis for organ involvement in SSc. The online version of this article (10.1186/s13075-018-1694-9) contains supplementary material, which is available to authorized users.
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影响因子：
27.4
作者：
Avouac, Jerome;Konstantinova, Irena;Allanore, Yannick
通讯作者：
Allanore, Yannick
影响因子：
4.4
作者：
Kavian, Niloufar;Marut, Wioleta;Batteux, Frederic
通讯作者：
Batteux, Frederic
影响因子：
13.3
作者：
Avouac, Jerome;Guignabert, Christophe;Allanore, Yannick
通讯作者：
Allanore, Yannick
影响因子：
4
作者：
Maurer, Britta;Distler, Joerg H. W.;Distler, Oliver
通讯作者：
Distler, Oliver
影响因子：
12.8
作者：
Eisenberg RA;Via CS
通讯作者：
Via CS