IL-21 accelerates xenogeneic graft-versus-host disease correlated with increased B-cell proliferation
IL-21 accelerates xenogeneic graft-versus-host disease correlated with increased B-cell proliferation
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IL-21 加速与 B 细胞增殖增加相关的异种移植物抗宿主病
DOI：
10.1007/s13238-013-3088-8
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发表时间：
2013-11
期刊：
影响因子：
--
通讯作者：
shengdian wang
中科院分区：
文献类型：
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作者：
xiaoran wu;yi tan;qiao xing;shengdian wang
移植物抗宿主病（GVHD）是造血干细胞移植常见的潜在并发症。异种移植物抗宿主病（X-GVHD）的动物模型，准确地模拟GVHD的临床表现，将提供一个工具，研究疾病的发病机制。小鼠模型表明，抑制IL-21信号传导是通过损害T细胞功能来减少GVHD的良好疗法。我们试图研究外源性人IL-21对X-GVHD过程的影响。在本研究中，通过流体动力学基因递送在静脉内移植人外周血单核细胞（hPBMC）的BALB/c-Rag 2 −/−IL-2 R Γc−/−（BRG）免疫缺陷小鼠中表达人IL-21。我们发现，人IL-21加剧了X-GVHD，并导致快速死亡。早在hPBMC移植到BRG小鼠后6天，在IL-21处理的小鼠的脾脏中观察到人CD 19 +B细胞而不是T细胞的显著扩增。与对照组相比，IL-21诱导了大量免疫球蛋白分泌，并伴随着脾脏中CD 19 + CD 38 highplasma细胞的增加。此外，我们证明了B细胞耗竭能够改善X-GVHD。这些结果首次发现人B细胞对IL-21的应答性体内扩增和分化，并揭示了B细胞扩增与异种GVHD恶化之间的相关性。我们的研究结果显示了B细胞参与X-GVHD的证据，并可能对该疾病的治疗产生影响。
Graft-versus-host disease (GVHD) is a prevalent and potential complication of hematopoietic stem cell transplantation. An animal model, xenogeneic GVHD (X-GVHD), that mimics accurately the clinical presentation of GVHD would provide a tool for investigating the mechanism involved in disease pathogenesis. Murine models indicated that inhibiting IL-21 signaling was a good therapy to reduce GVHD by impairing T cell functions. We sought to investigate the effect of exogenous human IL-21 on the process of X-GVHD. In this study, human IL-21 was expressed by hydrodynamic gene delivery in BALB/c-Rag2−/−IL-2RΓc−/−(BRG) immunodeficient mice which were intravenously transplanted human peripheral blood mononuclear cells (hPBMCs). We found that human IL-21 exacerbated X-GVHD and resulted in rapid fatality. As early as 6 days after hPBMCs transplanted to BRG mice, a marked expansion of human CD19+B cells, but not T cells, was observed in spleen of IL-21-treated mice. Compared with control group, IL-21 induced robust immunoglobulin secretion, which was accompanied by increased accumulation of CD19+CD38highplasma cells in spleen. In addition, we demonstrated that B-cell depletion was able to ameliorate X-GVHD. These results are the first to findin vivoexpansion and differentiation of human B cells in response to IL-21, and reveal a correlation between the expansion of B cells and the exacerbation of xenogeneic GVHD. Our findings show evidence of the involvement of B cells in X-GVHD and may have implications in the treatment of the disease.
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影响因子：
4.8
作者：
Meguro A;Ozaki K;Hatanaka K;Oh I;Sudo K;Ohmori T;Matsu H;Tatara R;Sato K;Sakata Y;Nakae S;Leonard WJ;Ozawa K
通讯作者：
Ozawa K
DOI：
10.1007/978-3-319-03218-4_36
发表时间：
2016
期刊：
--
影响因子：
--
作者：
H. Gloster;Lauren E. Gebauer;Rachel L. Mistur
通讯作者：
H. Gloster;Lauren E. Gebauer;Rachel L. Mistur
影响因子：
20.3
作者：
Hippen, Keli L.;Bucher, Christoph;Blazar, Bruce R.
通讯作者：
Blazar, Bruce R.
影响因子：
4.4
作者：
Good, Kim L.;Bryant, Vanessa L.;Tangye, Stuart G.
通讯作者：
Tangye, Stuart G.
DOI：
10.1038/nri3212
发表时间：
2012-05-11
期刊：
Nature reviews. Immunology
影响因子：
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作者：
通讯作者：
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