Tbet promotes CXCR6 expression in immature natural killer cells and natural killer cell egress from the bone marrow.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read Online Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Blackwell Scientific Publications Country of Publication: England NLM ID: 0374672 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2567 (Electronic) Linking ISSN: 00192805 NLM ISO Abbreviation: Immunology Subsets: MEDLINE
    • Publication Information:
      Original Publication: Oxford : Blackwell Scientific Publications
    • Subject Terms:
      Bone Marrow Cells/*metabolism ; Hematopoietic Stem Cells/*metabolism ; Killer Cells, Natural/*immunology ; Receptors, CXCR6/*metabolism ; T-Box Domain Proteins/*genetics; Animals ; Bone Marrow/metabolism ; Bone Marrow Transplantation ; Cell Movement/genetics ; Hematopoietic Stem Cells/cytology ; Killer Cells, Natural/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; T-Box Domain Proteins/metabolism
    • Abstract:
      Tbet-deficient mice have reduced natural killer (NK) cells in blood and spleen, but increased NK cells in bone marrow and lymph nodes, a phenotype that is thought to be the result of defective migration. Here, we revisit the role of Tbet in NK cell bone marrow egress. We definitively show that the accumulation of NK cells in the bone marrow of Tbet-deficient Tbx21 -/- animals occurs because of a migration defect and identify a module of genes, co-ordinated by Tbet, which affects the localization of NK cells in the bone marrow. Cxcr6 is approximately 125-fold underexpressed in Tbx21 -/- , compared with wild-type, immature NK cells. Immature NK cells accumulate in the bone marrow of CXCR6-deficient mice, and CXCR6-deficient progenitors are less able to reconstitute the peripheral NK cell compartment than their wild-type counterparts. However, the CXCR6 phenotype is largely confined to immature NK cells, whereas the Tbet phenotype is present in both immature and mature NK cells, suggesting that genes identified as being more differentially expressed in mature NK cells, such as S1pr5, Cx3cr1, Sell and Cd69, may be the major drivers of the phenotype.
      (© 2020 The Authors. Immunology published by John Wiley & Sons Ltd.)
    • References:
      Nat Immunol. 2009 Apr;10(4):403-11. (PMID: 19252491)
      Mediators Inflamm. 2015;2015:368427. (PMID: 26494947)
      Immunity. 2019 Apr 16;50(4):1054-1068.e3. (PMID: 30926235)
      J Immunol. 2013 Dec 1;191(11):5684-94. (PMID: 24184559)
      Trends Immunol. 2019 Feb;40(2):142-158. (PMID: 30639050)
      Eur J Immunol. 2017 Jun;47(6):946-953. (PMID: 28475283)
      Front Immunol. 2017 Feb 15;8:130. (PMID: 28261203)
      J Exp Med. 2015 Nov 16;212(12):2015-25. (PMID: 26503444)
      Trends Immunol. 2017 Apr;38(4):287-297. (PMID: 28279590)
      J Exp Med. 2014 Mar 10;211(3):563-77. (PMID: 24516120)
      J Exp Med. 2009 Oct 26;206(11):2469-81. (PMID: 19808259)
      Immunity. 2004 Apr;20(4):477-94. (PMID: 15084276)
      Nat Immunol. 2007 Dec;8(12):1337-44. (PMID: 17965716)
      Nat Immunol. 2002 Jun;3(6):523-8. (PMID: 12006976)
      Nat Rev Immunol. 2013 Feb;13(2):145-9. (PMID: 23348417)
      Cell. 2018 Aug 23;174(5):1054-1066. (PMID: 30142344)
      PLoS Biol. 2005 Apr;3(4):e113. (PMID: 15799695)
      PLoS One. 2016 Jun 09;11(6):e0157022. (PMID: 27280887)
      Elife. 2019 Aug 08;8:. (PMID: 31393266)
      Elife. 2014 Oct 13;3:. (PMID: 25310240)
      Elife. 2014 Jan 01;3:e01659. (PMID: 24714492)
      Nat Immunol. 2017 Sep;18(9):995-1003. (PMID: 28759002)
      Cell. 2000 Mar 17;100(6):655-69. (PMID: 10761931)
      Blood. 2009 May 28;113(22):5488-96. (PMID: 19234143)
      J Immunol. 2016 Feb 15;196(4):1449-54. (PMID: 26792802)
      Nat Immunol. 2017 Sep;18(9):1004-1015. (PMID: 28759001)
      Blood. 2011 Nov 3;118(18):4863-71. (PMID: 21911833)
      Blood. 2011 Nov 17;118(20):5439-47. (PMID: 21931117)
      Sci Rep. 2015 Jul 24;5:11664. (PMID: 26206182)
    • Grant Information:
      8_CE15-0024-01 Agence Nationale de la Recherche; WT105677 United Kingdom WT_ Wellcome Trust
    • Contributed Indexing:
      Keywords: CXCR6; Tbet; bone marrow; migration; natural killer cells
    • Accession Number:
      0 (Cxcr6 protein, mouse)
      0 (Receptors, CXCR6)
      0 (T-Box Domain Proteins)
      0 (T-box transcription factor TBX21)
    • Publication Date:
      Date Created: 20200509 Date Completed: 20210524 Latest Revision: 20210524
    • Publication Date:
      20221213
    • Accession Number:
      PMC7450165
    • Accession Number:
      10.1111/imm.13204
    • Accession Number:
      32383173