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Thomas, M.F.* ; Abdul-Wajid, S.* ; Panduro, M.* ; Babiarz, J.E.* ; Rajaram, M.* ; Woodruff, P.* ; Lanier, L.L.* ; Heissmeyer, V. ; Ansel, K.M.*

Eri1 regulates microRNA homeostasis and mouse lymphocyte development and anti-viral function.

Blood 120, 130-142 (2012)
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Natural killer (NK) cells play a critical role in early host defense to infected and transformed cells. Here we show that mice deficient in Eri1, a conserved 3'-to-5' exoribonuclease that represses RNA interference, have a cell-intrinsic defect in NK cell development and maturation. Eri1(-/-) NK cells displayed delayed acquisition of Ly49 receptors in the bone marrow and a selective reduction in Ly49D and Ly49H activating receptors in the periphery. Eri1 was required for immune-mediated control of mouse cytomegalovirus (MCMV) infection. Ly49H(+) NK cells deficient in Eri1 failed to expand efficiently during MCMV infection, and virus-specific responses were also diminished among Eri1(-/-) T cells. We identified miRNAs as the major endogenous small RNA target of Eri1 in mouse lymphocytes. Both NK and T cells deficient in Eri1 displayed a global, sequence-independent increase in miRNA abundance. Ectopic Eri1 expression rescued defective miRNA expression in mature Eri1(-/-) T cells. Thus, mouse Eri1 regulates miRNA homeostasis in lymphocytes and is required for normal NK cell development and anti-viral immunity.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Natural-killer-cells ; Murine Cytomegalovirus-infection ; Caenorhabditis-elegans ; Activation Receptor ; Gamma Production ; Viral-infection ; Cutting Edge ; C-elegans ; Nk ; Mice
Language
Publication Year 2012
HGF-reported in Year 2012
ISSN (print) / ISBN 0006-4971
e-ISSN 1528-0020
Journal Blood
Quellenangaben Volume: 120, Issue: 1, Pages: 130-142 Article Number: , Supplement: ,
Publisher American Society of Hematology
Reviewing status Peer reviewed
POF-Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s) Immune Response and Infection
PSP Element(s) G-501792-001
PubMed ID 22613798
Scopus ID 84863594456
Erfassungsdatum 2012-05-21