静止组织干细胞逃避免疫监视。
Quiescent Tissue Stem Cells Evade Immune Surveillance.
机构信息
Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
出版信息
Immunity. 2018 Feb 20;48(2):271-285.e5. doi: 10.1016/j.immuni.2018.02.001.
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.
干细胞对于许多组织的维持至关重要，但它们在面对免疫时的完整性是否得到维持尚不清楚。在这里，我们发现，包括 Lgr5 肠道干细胞在内的周期性上皮干细胞，以及卵巢和乳腺干细胞，会被活化的 T 细胞消除，但毛囊和肌肉中的静止干细胞对 T 细胞杀伤具有抗性。免疫逃避是静止干细胞的固有特性，这是由于抗原呈递机制（包括 MHC Ⅰ类和 TAP 蛋白）在全身水平下调所致，并且由转录激活因子 NLRC5 介导。这一过程在干细胞进入细胞周期时会被逆转。这些研究鉴定了干细胞静止、抗原呈递和免疫逃避之间的联系。由于起始癌症的细胞可以来源于干细胞，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。
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