Quiescent Tissue Stem Cells Evade Immune Surveillance

• Published in: Immunity (Cambridge, Mass.) Vol. 48; no. 2; pp. 271 - 285.e5
• Main Authors: Agudo, Judith, Park, Eun Sook, Rose, Samuel A., Alibo, Eziwoma, Sweeney, Robert, Dhainaut, Maxime, Kobayashi, Koichi S., Sachidanandam, Ravi, Baccarini, Alessia, Merad, Miriam, Brown, Brian D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.02.2018; Elsevier Limited
• Subjects: Animals; Antigen Presentation; Antigens; Cancer; Cell cycle; hair follicle; Hair Follicle - cytology; Homeostasis; Immune Evasion; immune privilege; Immune system; Immunity; Immunologic Surveillance; Immunology; Immunosurveillance; Intestine; Intracellular Signaling Peptides and Proteins - physiology; Killer Cells, Natural - immunology; Lymphocytes; Lymphocytes T; Machinery and equipment; Major histocompatibility complex; MHC class I; Mice; Mice, Inbred C57BL; Muscles; Muscles - cytology; Mutation; Nlrc5; Proteins; quiescence; Receptors, G-Protein-Coupled - physiology; Rodents; Stem cells; Stem Cells - immunology; Studies; Surveillance; T cell; T cell receptors; Tissues; Transplants & implants; Tumor Escape; United States > US; stem cells; intestine; antigen presentation; T cell; MHC class I; quiescence; hair follicle; Nlrc5; immunology; immune privilege
• ISSN: 1074-7613; 1097-4180; 1097-4180
• 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. [Display omitted] •Lgr5+ intestinal, ovary, and mammary stem cells are subject to T cell clearance•Hair follicle stem cells evade detection and killing by innate and adaptive immunity•Hair follicle stem cells downregulate Nlrc5 and MHC class I in their quiescent state•Expression of Nlrc5 upregulates MHC class I on hair follicle stem cells 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.