title: MicroRNAs and Their Targets Are Differentially Regulated in Adult and Neonatal Mouse CD8+ T Cells.
abstract: Immunological memory, which protects organisms from re-infection, is a hallmark of the mammalian adaptive immune system and the underlying principle of vaccination. In early life, however, mice and other mammals are deficient at generating memory CD8+ T cells, which protect organisms from intracellular pathogens. The molecular basis that differentiates adult and neonatal CD8+ T cells is unknown. MicroRNAs (miRNAs) are both developmentally regulated and required for normal adult CD8+ T cell functions. We used next-generation sequencing to identify mouse miRNAs that are differentially regulated in adult and neonatal CD8+ T cells, which may contribute to the impaired development of neonatal memory cells. The miRNA profiles of adult and neonatal cells were surprisingly similar during infection; however, we observed large differences prior to infection. In particular, miR-29 and miR-130 have significant differential expression between adult and neonatal cells before infection. Importantly, using RNA-Seq, we detected reciprocal changes in expression of messenger RNA targets for both miR-29 and miR-130. Moreover, targets that we validated include Eomes and Tbx21, key genes that regulate the formation of memory CD8+ T cells. Notably, age-dependent changes in miR-29 and miR-130 are conserved in human CD8+ T cells, further suggesting that these developmental differences are biologically relevant. Together, these results demonstrate that miR-29 and miR-130 are likely important regulators of memory CD8+ T cell formation and suggest that neonatal cells are committed to a short-lived effector cell fate prior to infection.
authors.affiliation: Graduate Field of Biochemistry, Molecular, and Cell Biology, Cornell University, Ithaca, New York 14853.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Wissink
authors.affiliation: Department of Microbiology and Immunology, Cornell University, Ithaca, New York 14853.
authors.forename: Norah L
authors.initials: NL
authors.lastname: Smith
authors.affiliation: Graduate Field of Genetics, Genomics, and Development, Cornell University, Ithaca, New York 14853.
authors.forename: Roman
authors.initials: R
authors.lastname: Spektor
authors.affiliation: Department of Microbiology and Immunology, Cornell University, Ithaca, New York 14853 bdr54@cornell.edu agrimson@cornell.edu.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Rudd
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853 bdr54@cornell.edu agrimson@cornell.edu.
authors.forename: Andrew
authors.initials: A
authors.lastname: Grimson
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000235:genetics / Q000276:immunology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007156:Immunologic Memory / Q000235:genetics; D007231:Infant, Newborn; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D055815:Young Adult
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger
keywords: adaptive immunity; development; microRNA regulation