title: miR-451 limits CD4+T cell proliferative responses to infection in mice.
abstract: MicroRNAs (miRNAs) are major regulators of cell responses, particularly in stressed cell states and host immune responses. Some miRNAs have a role in pathogen defense, including regulation of immune responses to Plasmodium parasite infection. Using a nonlethal mouse model of blood stage malaria infection, we have found that miR-451-/-mice infected with Plasmodium yoelii XNL cleared infection at a faster rate than did wild-type (WT) mice. MiR-451-/-mice had an increased leukocyte response to infection, with the protective phenotype primarily driven by CD4+T cells. WT and miR-451-/-CD4+T cells had similar activation responses, but miR-451-/-CD4+cells had significantly increased proliferation, both in vitro and in vivo. Myc is a miR-451 target with a central role in cell cycle progression and cell proliferation. CD4+T cells from miR-451-/-mice had increased postactivation Myc expression. RNA-Seq analysis of CD4+cells demonstrated over 5000 differentially expressed genes in miR-451-/-mice postinfection, many of which are directly or indirectly Myc regulated. This study demonstrates that miR-451 regulates T cell proliferative responses in part via a Myc-dependent mechanism.
authors.affiliation: Aab Cardiovascular Research Institute, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY, 14642, USA.|CTSI Translational Biomedical Science, Rochester, NY, USA.
authors.forename: Lesley M
authors.initials: LM
authors.lastname: Chapman
authors.affiliation: Aab Cardiovascular Research Institute, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY, 14642, USA.
authors.forename: Sara K
authors.initials: SK
authors.lastname: Ture
authors.affiliation: Aab Cardiovascular Research Institute, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY, 14642, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Field
authors.affiliation: Aab Cardiovascular Research Institute, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY, 14642, USA. Craig_Morrell@urmc.rochester.edu.
authors.forename: Craig N
authors.initials: CN
authors.lastname: Morrell
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002453:Cell Cycle; D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D008213:Lymphocyte Activation; D008288:Malaria / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D010967:Plasmodium yoelii / Q000276:immunology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs; C550758:Mirn451 microRNA, mouse; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc
keywords: Malaria; Proliferation; T cell; miRNA; myc