@article{31a0f597bceb46f7b7d68f4ab4f05d4d,
title = "Quiescent Tissue Stem Cells Evade Immune Surveillance",
abstract = "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. Agudo et al. find that cycling tissue stem cells are subject to immune clearance, but quiescent stem cells downregulate the antigen presentation machinery and evade immune surveillance.",
keywords = "MHC class I, Nlrc5, T cell, antigen presentation, hair follicle, immune privilege, immunology, intestine, quiescence, stem cells",
author = "Judith Agudo and Park, {Eun Sook} and Rose, {Samuel A.} and Eziwoma Alibo and Robert Sweeney and Maxime Dhainaut and Kobayashi, {Koichi S.} and Ravi Sachidanandam and Alessia Baccarini and Miriam Merad and Brown, {Brian D.}",
note = "Funding Information: We thank Marc Feldmann (U. Oxford), Daniel Schramek (U. Toronto), Ken Lau (Vanderbilt), Adeeb Rahman (Icahn School of Medicine), and Robert Krauss, Mark Lebwohl, and Emma Guttman (Mount Sinai) for helpful discussions and Albert Ruzo for technical assistance. B.D.B. and M.M. were supported by NIH R01AI104848, R01AI113221, R21OD020185, and R01DK106593. J.A. was supported by the Robin Chemers Neustein Award and a Juvenile Diabetes Research Foundation (JDRF) postdoctoral fellowship (3-2013-92). Funding Information: We thank Marc Feldmann (U. Oxford), Daniel Schramek (U. Toronto), Ken Lau (Vanderbilt), Adeeb Rahman (Icahn School of Medicine), and Robert Krauss, Mark Lebwohl, and Emma Guttman (Mount Sinai) for helpful discussions and Albert Ruzo for technical assistance. B.D.B. and M.M. were supported by NIH R01AI104848 , R01AI113221 , R21OD020185 , and R01DK106593 . J.A. was supported by the Robin Chemers Neustein Award and a Juvenile Diabetes Research Foundation (JDRF) postdoctoral fellowship ( 3-2013-92 ). Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",
year = "2018",
month = feb,
day = "20",
doi = "10.1016/j.immuni.2018.02.001",
language = "English",
volume = "48",
pages = "271--285.e5",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "2",
}