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Blood, 25 June 2009, Vol. 113, No. 26, pp. 6648-6657. Prepublished online as a Blood First Edition Paper on March 13, 2009; DOI 10.1182/blood-2008-09-181156. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-09-181156v1 113/26/6648    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Google Scholar Articles by Weitzel, R. P. Articles by Laughlin, M. J. PubMed PubMed Citation Articles by Weitzel, R. P. Articles by Laughlin, M. J. Related Collections Immunobiology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY microRNA 184 regulates expression of NFAT1 in umbilical cord blood CD4+ T cells R. Patrick Weitzel1,2, Mathew L. Lesniewski1, Peter Haviernik1, Suzanne Kadereit3, Patrick Leahy4, Nicholas J. Greco1,4,5, and Mary J. Laughlin1,2,4,5 Departments of 1 Medicine and 2 Pathology, Case Western Reserve University, Cleveland, OH; 3 Department of Biology, University of Konstanz, Konstanz, Germany; 4 Case Comprehensive Cancer Center, Cleveland, OH; and 5 Abraham J. and Phyllis Katz Cord Blood Foundation, Cleveland Cord Blood Center, OH The reduced expression of nuclear factor of activated T cells-1 (NFAT1) protein in umbilical cord blood (UCB)–derived CD4+ T cells and the corresponding reduction in inflammatory cytokine secretion after stimulation in part underlies their phenotypic differences from adult blood (AB) CD4+ T cells. This muted response may contribute to the lower incidence and severity of high-grade acute graft-versus-host disease (aGVHD) exhibited by UCB grafts. Here we provide evidence that a specific microRNA, miR-184, inhibits NFAT1 protein expression elicited by UCB CD4+ T cells. Endogenous expression of miR-184 in UCB is 58.4-fold higher compared with AB CD4+ T cells, and miR-184 blocks production of NFAT1 protein through its complementary target sequence on the NFATc2 mRNA without transcript degradation. Furthermore, its negative effects on NFAT1 protein and downstream interleukin-2 (IL-2) transcription are reversed through antisense blocking in UCB and can be replicated via exogenous transfection of precursor miR-184 into AB CD4+ T cells. Our findings reveal a previously uncharacterized role for miR-184 in UCB CD4+ T cells and a novel function for microRNA in the early adaptive immune response. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: UCB transplantation: miRNA involvement Pablo Landgraf Blood 2009 113: 6505-6506. [Full Text] [PDF] This article has been cited by other articles: P. Landgraf UCB transplantation: miRNA involvement Blood, June 25, 2009; 113(26): 6505 - 6506. [Full Text] [PDF]

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