title: miR-150 Regulates Differentiation and Cytolytic Effector Function in CD8+ T cells.
abstract: MicroRNAs regulate most mammalian genes, and they control numerous aspects of immune system development and function. Their precise roles in the CD8+ T cell response, however, remain unclear. In this report, we show that in the absence of the microRNA miR-150, CD8+ T cells fail to undergo robust expansion and differentiation into short-lived terminal effector cells in response to primary infection with Listeria monocytogenes or Vaccinia virus. Notably, even after transitioning into the memory pool, miR-150(-/-) cells still mount a weaker recall response to secondary infection, and remain less differentiated than their wild-type counterparts. Transcriptome analysis shows miR-150 gene targets are globally upregulated in cells lacking miR-150, and amongst these targets, we found misregulation of genes associated with proliferation and effector cell function. These transcriptome data suggest that miR-150 deficient CD8+ T cells are less efficient in killing infected cells, which we validate experimentally. Together, these results reveal a cell-intrinsic role for miR-150 in the regulation of effector CD8+ T cell fate and function.
authors.affiliation: Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853.
authors.forename: Norah L
authors.initials: NL
authors.lastname: Smith
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Wissink
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853.
authors.forename: Andrew
authors.initials: A
authors.lastname: Grimson
authors.affiliation: Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Rudd
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics*; D003602:Cytotoxicity, Immunologic / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D007156:Immunologic Memory / Q000235:genetics; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D010641:Phenotype; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: D035683:MicroRNAs; C533097:MIR150, human