title: Differential chemotactic receptor requirements for NK cell subset trafficking into bone marrow.
abstract: Responsiveness of maturing natural killer (NK) cells to chemotactic molecules directly affect their retention and relocation in selected bone marrow (BM) microenvironment during development, as well as their localization at sites of immune response during inflammatory diseases. BM is the main site of NK cell generation, providing microenvironmental signals required to sustain cell proliferation and differentiation. Drastic changes of expression and function of several chemoattractant receptors can be observed during progression from precursor NK cells to immature and mature NK cells. Indeed, the gradual decrease of CXCR4 expression parallels the increased expression of CXCR3, CCR1, and CX3CR1 and S1P(5) (Sphingosine-1-phosphate receptor 5) on mature DX5(+) NK cells. The chemokine CXCL12 is produced constitutively in the BM and, acting via CXCR4, is critical for retaining immature and mature NK cell subsets in the BM. During steady-state, the maintenance of NK cells into BM parenchyma depends on the equilibrium of CXCR4 retention and S1P(5) mobilizing functions, as the gradient of S1P coming from the sinusoids facilitates mature NK cell egress into circulation via S1P(5), when CXCR4/CXCL12-mediated retention decreases. Chemoattractants are also key factors for the response to inflammatory or infection conditions that promote mobilization of effector NK cells from storage compartments (including BM) to sites of disease or for NK cell recruitment/response during pathological conditions that affect BM integrity, including hematopoietic malignancies. In this review, we summarize what is known about the requirement for NK cell localization and exit from BM and how chemokine-mediated functions may affect BM NK cell development and immune responses.
authors: Laboratory of Immunology and Immunopathology, Department of Molecular Medicine and Istituto Pasteur-Fondazione Cenci Bolognetti, "Sapienza" Università di Roma Rome, Italy.
authors: Giovanni
authors: G
authors: Bernardini
authors: Giuseppe
authors: G
authors: Sciumè
authors: Angela
authors: A
authors: Santoni
keywords: NK cells; bone marrow; chemokines; egress; trafficking
references: Exp Hematol. 2007 Dec;35(12):1839-46
references: 18036444
references: Nat Immunol. 2006 Nov;7(11):1217-24
references: 17013389
references: J Immunol. 2005 Feb 1;174(3):1213-21
references: 15661875
references: J Immunol. 2003 Nov 15;171(10):5085-90
references: 14607906
references: J Immunol. 2006 Apr 15;176(8):4716-29
references: 16585565
references: Blood. 2002 Sep 15;100(6):1935-47
references: 12200350
references: Blood. 2008 Apr 1;111(7):3626-34
references: 18227348
references: Immunol Rev. 2000 Apr;174:5-20
references: 10807503
references: Clin Exp Immunol. 1999 May;116(2):371-8
references: 10337033
references: J Immunol. 2007 Apr 15;178(8):4764-70
references: 17404256
references: J Immunol. 2006 Feb 1;176(3):1517-24
references: 16424180
references: Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):13028-33
references: 20615964
references: J Immunol. 1979 Oct;123(4):1832-8
references: 383842
references: Ann Rheum Dis. 2006 Mar;65(3):294-300
references: 16107514
references: Nat Immunol. 2006 Mar;7(3):311-7
references: 16462739
references: J Immunol. 1999 Jun 1;162(11):6658-62
references: 10352283
references: Nat Med. 2012 Aug;18(8):1224-31
references: 22820642
references: J Surg Res. 1990 May;48(5):448-53
references: 2352420
references: Br J Haematol. 2002 Dec;119(3):660-4
references: 12437641
references: Cancer Res. 2008 Mar 15;68(6):1715-22
references: 18339851
references: Immunity. 2004 Jun;20(6):707-18
references: 15189736
references: Immunol Lett. 2012 Jul 30;145(1-2):39-46
references: 22698182
references: Blood. 2003 Sep 15;102(6):1951-8
references: 12730102
references: Nat Immunol. 2010 Dec;11(12):1127-35
references: 20972432
references: Cell Host Microbe. 2009 Dec 17;6(6):503-12
references: 20006839
references: Blood. 2011 Apr 28;117(17):4467-75
references: 21364193
references: Blood. 2008 Aug 1;112(3):461-9
references: 18650461
references: Eur J Immunol. 2001 Jun;31(6):1900-9
references: 11433387
references: J Immunol. 1979 Jun;122(6):2541-7
references: 376736
references: J Immunol. 2012 Sep 1;189(5):2333-7
references: 22821961
references: Blood. 1999 Jul 1;94(1):333-9
references: 10381530
references: Nat Rev Immunol. 2008 Apr;8(4):259-68
references: 18340344
references: J Immunol. 2009 Sep 1;183(5):3219-28
references: 19657090
references: J Immunol. 2005 Jun 15;174(12):7654-64
references: 15944266
references: Clin Immunol Immunopathol. 1996 Dec;81(3):277-81
references: 8938105
references: Blood. 2003 Apr 15;101(8):3052-7
references: 12480696
references: Immunity. 2011 Apr 22;34(4):590-601
references: 21458307
references: Arthritis Rheum. 2010 Dec;62(12):3799-805
references: 20848566
references: Nat Rev Immunol. 2003 May;3(5):413-25
references: 12766763
references: J Immunol. 2002 Mar 15;168(6):2585-9
references: 11884419
references: Immunity. 2003 Oct;19(4):583-93
references: 14563322
references: Blood. 2011 Jan 13;117(2):451-8
references: 20944068
references: Eur J Immunol. 2008 Nov;38(11):2946-8
references: 18979517
references: J Immunol. 1996 Oct 1;157(7):3054-64
references: 8816415
references: Blood. 2001 May 15;97(10):3146-51
references: 11342442
references: Nat Immunol. 2007 Dec;8(12):1337-44
references: 17965716
references: Blood. 2011 Apr 21;117(16):4349-57
references: 21224471
references: Front Biosci (Landmark Ed). 2009 Jan 01;14:540-51
references: 19273084
references: Blood. 1998 Mar 1;91(5):1706-15
references: 9473237
references: Haematologica. 2006 Nov;91(11):1489-97
references: 17082008
references: Immunity. 2012 Jan 27;36(1):55-67
references: 22261438
references: Blood. 2001 Jun 1;97(11):3349-53
references: 11369623
references: Nat Immunol. 2002 Jul;3(7):687-94
references: 12068293
references: Immunol Rev. 2007 Dec;220:169-82
references: 17979846
references: Blood. 2005 Mar 1;105(5):2082-9
references: 15536146
references: Blood. 2011 Nov 3;118(18):4863-71
references: 21911833
references: Nat Immunol. 2002 Jun;3(6):523-8
references: 12006976
references: J Exp Med. 2009 Sep 28;206(10):2235-51
references: 19720840
references: Annu Rev Immunol. 2012;30:69-94
references: 22149932