NOD2 regulates hematopoietic cell function during graft-versus-host disease.
NOD2 regulates hematopoietic cell function during graft-versus-host disease.
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DOI：
10.1084/jem.20090623
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发表时间：
2009-09-28
期刊：
影响因子：
--
通讯作者：
van den Brink MR
中科院分区：
文献类型：
--
作者：
Penack O;Smith OM;Cunningham-Bussel A;Liu X;Rao U;Yim N;Na IK;Holland AM;Ghosh A;Lu SX;Jenq RR;Liu C;Murphy GF;Brandl K;van den Brink MR
核苷酸结合寡聚化结构域2 （NOD2）多态性是克罗恩病和移植物抗宿主病（GVHD）的独立危险因素。在克罗恩病中，由NOD2突变引起的促炎状态与肠细胞（如paneth细胞）抗菌功能的丧失有关。NOD2在实验性同种异体骨髓移植（alloo - bmt）中尚未被研究。通过使用NOD2 - / -造血细胞嵌合受体，我们证明了宿主造血细胞中NOD2缺乏会加剧GVHD。我们发现，在NOD2缺失的异源bmt受体中，供体T细胞的增殖和激活增强，这表明NOD2在宿主抗原呈递细胞（APCs）的调节中起作用。接下来，我们在实验性结肠炎模型中使用骨髓嵌合体，再次观察到造血细胞中NOD2缺乏导致肠道炎症增加。我们认为NOD2通过抑制宿主APC功能调控GVHD的发生。
Nucleotide-binding oligomerization domain 2 (NOD2) polymorphisms are independent risk factors for Crohn's disease and graft-versus-host disease (GVHD). In Crohn's disease, the proinflammatory state resulting from NOD2 mutations have been associated with a loss of antibacterial function of enterocytes such as paneth cells. NOD2 has not been studied in experimental allogeneic bone marrow transplantation (allo-BMT). Using chimeric recipients with NOD2−/− hematopoietic cells, we demonstrate that NOD2 deficiency in host hematopoietic cells exacerbates GVHD. We found that proliferation and activation of donor T cells was enhanced in NOD-deficient allo-BMT recipients, suggesting that NOD2 plays a role in the regulation of host antigen-presenting cells (APCs). Next, we used bone marrow chimeras in an experimental colitis model and observed again that NOD2 deficiency in the hematopoietic cells results in increased intestinal inflammation. We conclude that NOD2 regulates the development of GVHD through its inhibitory effect on host APC function.
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影响因子：
46.9
作者：
Zakrzewski, Johannes L.;Suh, David;van den Brink, Marcel R. M.
通讯作者：
van den Brink, Marcel R. M.
影响因子：
4.8
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
32.4
作者：
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通讯作者：
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影响因子：
64.8
作者：
Ogura, Y;Bonen, DK;Cho, JH
通讯作者：
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