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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 (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 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 Citing Articles via Google Scholar Google Scholar Articles by Weitzel, R. P. Articles by Laughlin, M. J. Search for Related Content PubMed PubMed Citation Articles by Weitzel, R. P. Articles by Laughlin, M. J. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 29, 2008 Accepted March 6, 2009 MicroRNA 184 regulates expression of NFAT1 in umbilical cord blood CD4+ T-cells R. Patrick Weitzel, Mathew L. Lesniewski, Peter Haviernik, Suzanne Kadereit, Patrick Leahy, Nicholas J. Greco, and Mary J. Laughlin* Department of Medicine, Case Western Reserve University, Cleveland, OH, United States Department of Biology, University of Konstanz, Konstanz, Germany Case Comprehensive Cancer Center, Cleveland, OH, United States Abraham J & Phyllis Katz Cord Blood Foundation, Cleveland Cord Blood Center, Cleveland, OH, United States Department of Pathology, Case Western Reserve University, Cleveland, OH, United States * Corresponding author; email: mary.laughlin{at}case.edu. The reduced expression of NFAT1 protein in Umbilical Cord Blood (UCB)-derived CD4+ T-cells and the corresponding reduction in inflammatory cytokine secretion following 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 to 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 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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