Interleukin-22 protects intestinal stem cells from immune-mediated tissue damage and regulates sensitivity to graft versus host disease.
Interleukin-22 protects intestinal stem cells from immune-mediated tissue damage and regulates sensitivity to graft versus host disease.
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DOI：
10.1016/j.immuni.2012.05.028
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发表时间：
2012-08-24
期刊：
影响因子：
32.4
通讯作者：
van den Brink MR
中科院分区：
文献类型：
--
作者：
Hanash AM;Dudakov JA;Hua G;O'Connor MH;Young LF;Singer NV;West ML;Jenq RR;Holland AM;Kappel LW;Ghosh A;Tsai JJ;Rao UK;Yim NL;Smith OM;Velardi E;Hawryluk EB;Murphy GF;Liu C;Fouser LA;Kolesnick R;Blazar BR;van den Brink MR
关于在免疫介导的组织损伤期间肠干细胞（ISCs）和祖细胞的维持或关于移植受体在移植物抗宿主病（GVHD）期间对供体免疫系统介导的组织损伤的易感性知之甚少。我们在这里证明，缺乏免疫原性的IL-22增加急性GVHD组织损伤和死亡率，在GVHD期间ISCs被消除，并且ISCs及其下游祖细胞表达IL-22受体。肠IL-22产生骨髓移植后的IL-23-反应性先天淋巴细胞（ILC）从移植受体，肠IL-22增加，在移植前的条件。然而，ILC频率和IL-22量降低GVHD。IL-22缺乏导致隐窝细胞凋亡增加、ISCs耗竭和上皮完整性丧失。我们的研究结果表明，IL-22作为组织对GVHD敏感性的关键调节因子，在炎症性肠损伤期间是ISC的保护因子。
Little is known about the maintenance of intestinal stem cells (ISCs) and progenitors during immune-mediated tissue damage or about the susceptibility of transplant recipients to tissue damage mediated by the donor immune system during graft vs. host disease (GVHD). We demonstrate here that deficiency of recipient-derived IL-22 increased acute GVHD tissue damage and mortality, that ISCs were eliminated during GVHD, and that ISCs as well as their downstream progenitors expressed the IL-22 receptor. Intestinal IL-22 was produced after bone marrow transplant by IL-23-responsive innate lymphoid cells (ILCs) from the transplant recipients, and intestinal IL-22 increased in response to pre-transplant conditioning. However, ILC frequency and IL-22 amounts were decreased by GVHD. Recipient IL-22 deficiency led to increased crypt apoptosis, depletion of ISCs, and loss of epithelial integrity. Our findings reveal IL-22 as a critical regulator of tissue sensitivity to GVHD and a protective factor for ISC during inflammatory intestinal damage.
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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：
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DOI：
10.1073/pnas.1013004108
发表时间：
2011-01-04
影响因子：
11.1
作者：
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通讯作者：
Breault, David T.