MiR-150 Regulates the Development of NK and INKT Cells

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2011 Nov 30

PMID 22124110

Citations 129

Authors

Natalie A Bezman

Tirtha Chakraborty

Timothy Bender

Lewis L Lanier

Affiliations

Soon will be listed here.

Abstract

Natural killer (NK) and invariant NK T (iNKT) cells are critical in host defense against pathogens and for the initiation of adaptive immune responses. miRNAs play important roles in NK and iNKT cell development, maturation, and function, but the roles of specific miRNAs are unclear. We show that modulation of miR-150 expression levels has a differential effect on NK and iNKT cell development. Mice with a targeted deletion of miR-150 have an impaired, cell lineage-intrinsic defect in their ability to generate mature NK cells. Conversely, a gain-of-function miR-150 transgene promotes the development of NK cells, which display a more mature phenotype and are more responsive to activation. In contrast, overexpression of miR-150 results in a substantial reduction of iNKT cells in the thymus and in the peripheral lymphoid organs. The transcription factor c-Myb has been shown to be a direct target of miR-150. Our finding of increased NK cell and decreased iNKT cell frequencies in Myb heterozygous bone marrow chimeras suggests that miR-150 differentially controls the development of NK and iNKT cell lineages by targeting c-Myb.

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References

Gilmour K, Fujii H, Cranston T, Davies E, Kinnon C, Gaspar H . Defective expression of the interleukin-2/interleukin-15 receptor beta subunit leads to a natural killer cell-deficient form of severe combined immunodeficiency. Blood. 2001; 98(3):877-9. DOI: 10.1182/blood.v98.3.877. View

Hu T, Simmons A, Yuan J, Bender T, Alberola-Ila J . The transcription factor c-Myb primes CD4+CD8+ immature thymocytes for selection into the iNKT lineage. Nat Immunol. 2010; 11(5):435-41. PMC: 2857587. DOI: 10.1038/ni.1865. View

Matsuda J, Gapin L, Sidobre S, Kieper W, Tan J, Ceredig R . Homeostasis of V alpha 14i NKT cells. Nat Immunol. 2002; 3(10):966-74. DOI: 10.1038/ni837. View

Zhou X, Jeker L, Fife B, Zhu S, Anderson M, McManus M . Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity. J Exp Med. 2008; 205(9):1983-91. PMC: 2526194. DOI: 10.1084/jem.20080707. View

Li P, Burke S, Wang J, Chen X, Ortiz M, Lee S . Reprogramming of T cells to natural killer-like cells upon Bcl11b deletion. Science. 2010; 329(5987):85-9. PMC: 3628452. DOI: 10.1126/science.1188063. View

Gapin L, Matsuda J, Surh C, Kronenberg M . NKT cells derive from double-positive thymocytes that are positively selected by CD1d. Nat Immunol. 2001; 2(10):971-8. DOI: 10.1038/ni710. View

Bender T, Kremer C, Kraus M, Buch T, Rajewsky K . Critical functions for c-Myb at three checkpoints during thymocyte development. Nat Immunol. 2004; 5(7):721-9. DOI: 10.1038/ni1085. View

Fedeli M, Napolitano A, Wong M, Marcais A, De Lalla C, Colucci F . Dicer-dependent microRNA pathway controls invariant NKT cell development. J Immunol. 2009; 183(4):2506-12. DOI: 10.4049/jimmunol.0901361. View

Koralov S, Muljo S, Galler G, Krek A, Chakraborty T, Kanellopoulou C . Dicer ablation affects antibody diversity and cell survival in the B lymphocyte lineage. Cell. 2008; 132(5):860-74. DOI: 10.1016/j.cell.2008.02.020. View

10.

Orr M, Lanier L . Inhibitory Ly49 receptors on mouse natural killer cells. Curr Top Microbiol Immunol. 2010; 350:67-87. DOI: 10.1007/82_2010_85. View

11.

Xiao C, Calado D, Galler G, Thai T, Patterson H, Wang J . MiR-150 controls B cell differentiation by targeting the transcription factor c-Myb. Cell. 2007; 131(1):146-59. DOI: 10.1016/j.cell.2007.07.021. View

12.

Matsuda J, Naidenko O, Gapin L, Nakayama T, Taniguchi M, Wang C . Tracking the response of natural killer T cells to a glycolipid antigen using CD1d tetramers. J Exp Med. 2000; 192(5):741-54. PMC: 2193268. DOI: 10.1084/jem.192.5.741. View

13.

DiSanto J, Muller W, Fischer A, Rajewsky K . Lymphoid development in mice with a targeted deletion of the interleukin 2 receptor gamma chain. Proc Natl Acad Sci U S A. 1995; 92(2):377-81. PMC: 42743. DOI: 10.1073/pnas.92.2.377. View

14.

Smith H, Heusel J, Mehta I, Kim S, Dorner B, Naidenko O . Recognition of a virus-encoded ligand by a natural killer cell activation receptor. Proc Natl Acad Sci U S A. 2002; 99(13):8826-31. PMC: 124383. DOI: 10.1073/pnas.092258599. View

15.

Liston A, Lu L, OCarroll D, Tarakhovsky A, Rudensky A . Dicer-dependent microRNA pathway safeguards regulatory T cell function. J Exp Med. 2008; 205(9):1993-2004. PMC: 2526195. DOI: 10.1084/jem.20081062. View

16.

Lu J, Guo S, Ebert B, Zhang H, Peng X, Bosco J . MicroRNA-mediated control of cell fate in megakaryocyte-erythrocyte progenitors. Dev Cell. 2008; 14(6):843-53. PMC: 2688789. DOI: 10.1016/j.devcel.2008.03.012. View

17.

Zhou B, Wang S, Mayr C, Bartel D, Lodish H . miR-150, a microRNA expressed in mature B and T cells, blocks early B cell development when expressed prematurely. Proc Natl Acad Sci U S A. 2007; 104(17):7080-5. PMC: 1855395. DOI: 10.1073/pnas.0702409104. View

18.

Lin Y, Kuo M, Yu J, Kuo H, Lin R, Lo W . c-Myb is an evolutionary conserved miR-150 target and miR-150/c-Myb interaction is important for embryonic development. Mol Biol Evol. 2008; 25(10):2189-98. DOI: 10.1093/molbev/msn165. View

19.

Kunz B, HELD W . Positive and negative roles of the trans-acting T cell factor-1 for the acquisition of distinct Ly-49 MHC class I receptors by NK cells. J Immunol. 2001; 166(10):6181-7. DOI: 10.4049/jimmunol.166.10.6181. View

20.

Eckelhart E, Warsch W, Zebedin E, Simma O, Stoiber D, Kolbe T . A novel Ncr1-Cre mouse reveals the essential role of STAT5 for NK-cell survival and development. Blood. 2010; 117(5):1565-73. DOI: 10.1182/blood-2010-06-291633. View