Quiescent Tissue Stem Cells Evade Immune Surveillance.

Quiescent Tissue Stem Cells Evade Immune Surveillance.
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DOI:
10.1016/j.immuni.2018.02.001
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发表时间:
2018-02-20
期刊:
影响因子:
32.4
通讯作者:
Brown BD
Brown BD
中科院分区:
医学1区
文献类型:
--
作者:
Agudo J;Park ES;Rose SA;Alibo E;Sweeney R;Dhainaut M;Kobayashi KS;Sachidanandam R;Baccarini A;Merad M;Brown BD

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干细胞对于许多组织的维持至关重要,但在免疫力面前是否保持其完整性尚不清楚。在这里,我们发现循环上皮干细胞,包括Lgr 5+肠干细胞,以及卵巢和乳腺干细胞,被激活的T细胞清除,但毛囊和肌肉中的静止干细胞对T细胞杀伤有抵抗力。免疫逃避是由抗原呈递机制(包括MHC I类和Tap蛋白)的系统性下调引起的静止干细胞的固有特性,并且由反式激活因子Nlrc 5介导。这个过程在干细胞进入细胞周期后逆转。这些研究确定了干细胞静止、抗原呈递和免疫逃避之间的联系。由于癌症起始细胞可以来自干细胞,这些发现可能有助于解释最早的癌细胞如何逃避免疫监视。
Stem cells are critical for the maintenance of many tissues, but whether their integrity is maintained in the face of immunity is unclear. Here we found that cycling epithelial stem cells, including Lgr5+ intestinal stem cells, as well as ovary and mammary stem cells, were eliminated by activated T cells, but quiescent stem cells in the hair follicle and muscle were resistant to T cell killing. Immune evasion was an intrinsic property of the quiescent stem cells resulting from systemic downregulation of the antigen presentation machinery, including MHC class I and Tap proteins, and is mediated by the transactivator Nlrc5. This process was reversed upon stem cell entry into the cell cycle. These studies identify a link between stem cell quiescence, antigen presentation, and immune evasion. As cancer-initiating cells can derive from stem cells, these findings may help explain how the earliest cancer cells evade immune surveillance.
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