A modified graft-versus-host-induced model for systemic sclerosis, with pulmonary fibrosis in Rag2-deficient mice.
A modified graft-versus-host-induced model for systemic sclerosis, with pulmonary fibrosis in Rag2-deficient mice.
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Rag2 缺陷小鼠的改良移植物抗宿主诱导系统性硬化症模型，伴有肺纤维化
DOI：
10.1002/2211-5463.12268
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发表时间：
2017-09
期刊：
影响因子：
2.6
通讯作者：
Zou H
中科院分区：
文献类型：
--
作者：
Yang X;Liu C;Fujino M;Yang J;Li XK;Zou H
系统性硬化症（SSc）是一种导致多器官纤维化的结缔组织疾病。已经开发了用于这种疾病的各种动物模型，包括遗传的和诱导的。其中一种诱导模型，硬皮病移植物抗宿主病（scl-GvHD），表现出SSc的主要特征，但涉及受体的致死性γ辐射。我们试图开发一种改良的scl-GvHD模型。将来自B10.D2供体小鼠的脾细胞移植到BALB/c遗传背景的免疫缺陷Rag-2受体中。在移植后3周和9周分析组织纤维化。除了抗Scl-70自身抗体和细胞因子的血清水平、组织炎症、纤维化、I型胶原和α-平滑肌肌动蛋白（α-SMA）的表达、白细胞浸润、转化生长因子（TGF）-β、I型胶原、α-SMA、肿瘤坏死因子（TNF）-α和白细胞介素（IL）-6的mRNA表达外，还分析了组织中TGF-β、Smad-3和p-Smad-3表达的经典信号通路。在改良scl-GvHD小鼠模型的皮肤、肾脏和肺中可检测到皮肤增厚和胶原蛋白合成增加，以及组织纤维化的表现。可检测到抗Scl-70自身抗体、IL-10和TGF-β的血清水平升高。在皮肤、肾脏和肺中发现CD 4 + T细胞和F4/80+巨噬细胞浸润增加。在scl-GvHD模型的组织中，I型胶原、TGF-β、α-SMA、TNF-α和IL-6的基因表达增加。此外，在scl-GvHD小鼠的皮肤、肾脏和肺中检测到TGF-β表达和Smad-3磷酸化。我们的数据表明，将来自B10.D2供体小鼠的脾细胞移植到免疫缺陷Rag-2受体中不仅可以诱导皮肤和肾脏的典型纤维化，还可以诱导肺的典型纤维化，这在以前的scl-GvHD模型中是缺失的。因此，改良的scl-GvHD模型可能是一个有前途的模型，以探讨SSc的免疫机制，并可能是有用的研究新的治疗系统性硬化症。
Systemic sclerosis (SSc) is a connective tissue disease that results in fibrosis in multiple organs. Various animal models for this disease have been developed, both genetic and induced. One of the induced models, sclerodermatous graft‐versus‐host disease (scl‐GvHD), exhibits the main characteristics of SSc, but involves lethal γ‐irradiation of recipients. We sought to develop a modified scl‐GvHD model. Spleen cells from B10.D2 donor mice were transplanted into immunodeficient Rag‐2 recipients on the BALB/c genetic background. Tissue fibrosis was analyzed at 3 and 9 weeks after transplantation. In addition to serum levels of anti‐Scl‐70 autoantibody and cytokines, tissue inflammation, fibrosis, expression of collagen‐I and α‐smooth muscle actin (α‐SMA), infiltration of leukocytes, mRNA expression of transforming growth factor (TGF)‐β, collagen‐I, α‐SMA, tumor necrosis factor (TNF)‐α, and interleukin (IL)‐6, the classical signal pathway of TGF‐β, Smad‐3, and p‐Smad‐3 expression in tissue were analyzed. Skin thickening and increased collagen synthesis, as well as the manifestation of tissue fibrosis, could be detected in skin, kidney, and lung of modified scl‐GvHD mouse model. Increased serum levels of anti‐Scl‐70 autoantibody, IL‐10, and TGF‐β could be detected. Increased CD4+ T cells and F4/80+ macrophage infiltration were found in skin, kidney, and lung. Gene expression of collagen‐I, TGF‐β, α‐SMA, TNF‐α, and IL‐6 was increased in tissue of the scl‐GvHD model. Moreover, TGF‐β expression and Smad‐3 phosphorylation were detected in skin, kidney, and lung of scl‐GvHD mice. Our data show that spleen cells from B10.D2 donor mice transplanted into immunodeficient Rag‐2 recipients could induce typical fibrosis not only of the skin and kidney but also of lung, which was missing from previous scl‐GvHD models. Thus, the modified scl‐GvHD model might be a promising model to explore the immunologic mechanisms of SSc and may be useful for investigation of new therapies for systemic sclerosis.
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影响因子：
2
作者：
López-Briones, S;Lamoyi, E;Sciutto, E
通讯作者：
Sciutto, E
影响因子：
--
作者：
Coletti D;Berardi E;Aulino P;Rossi E;Moresi V;Li Z;Adamo S
通讯作者：
Adamo S
影响因子：
3.1
作者：
Fragoso, G;Lamoyi, E;Sciutto, E
通讯作者：
Sciutto, E
DOI：
10.1084/jem.20140643
发表时间：
2015-01-12
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chen C;Akiyama K;Wang D;Xu X;Li B;Moshaverinia A;Brombacher F;Sun L;Shi S
通讯作者：
Shi S
影响因子：
4.9
作者：
Desallais L;Avouac J;Fréchet M;Elhai M;Ratsimandresy R;Montes M;Mouhsine H;Do H;Zagury JF;Allanore Y
通讯作者：
Allanore Y