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• W2736096687 abstract "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." @default.
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• W2736096687 date "2017-08-16" @default.
• W2736096687 modified "2023-10-16" @default.
• W2736096687 title "A modified graft‐versus‐host‐induced model for systemic sclerosis, with pulmonary fibrosis in Rag2‐deficient mice" @default.
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• W2736096687 doi "https://doi.org/10.1002/2211-5463.12268" @default.
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