Interleukin-15-activated natural killer cells kill autologous osteoclasts via LFA-1, DNAM-1 and TRAIL, and inhibit osteoclast-mediated bone erosion in vitro.

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

Original Publication: Oxford : Blackwell Scientific Publications

Antigens, Differentiation, T-Lymphocyte/*immunology ; Interleukin-15/*immunology ; Killer Cells, Natural/*immunology ; Lymphocyte Function-Associated Antigen-1/*immunology ; Osteoclasts/*immunology ; TNF-Related Apoptosis-Inducing Ligand/*immunology; Apoptosis/immunology ; Bone Resorption/immunology ; Cell Communication/immunology ; Cell Differentiation/immunology ; Cell Survival/immunology ; Cells, Cultured ; Coculture Techniques ; Cytotoxicity, Immunologic/immunology ; Flow Cytometry ; Humans ; Interleukin-15/pharmacology ; Killer Cells, Natural/cytology ; Killer Cells, Natural/metabolism ; Lymphocyte Activation/drug effects ; Lymphocyte Activation/immunology ; Monocytes/cytology ; Monocytes/immunology ; Monocytes/metabolism ; Osteoclasts/cytology ; Osteoclasts/metabolism

Osteoclasts reside on bone and are the main bone resorbing cells playing an important role in bone homeostasis, while natural killer (NK) cells are bone-marrow-derived cells known to play a crucial role in immune defence against viral infections. Although mature NK cells traffic through bone marrow as well as to inflammatory sites associated with enhanced bone erosion, including the joints of patients with rheumatoid arthritis, little is known about the impact NK cells may have on mature osteoclasts and bone erosion. We studied the interaction between human NK cells and autologous monocyte-derived osteoclasts from healthy donors in vitro. We show that osteoclasts express numerous ligands for receptors present on activated NK cells. Co-culture experiments revealed that interleukin-15-activated, but not resting, NK cells trigger osteoclast apoptosis in a dose-dependent manner, resulting in drastically decreased bone erosion. Suppression of bone erosion requires contact between NK cells and osteoclasts, but soluble factors also play a minor role. Antibodies masking leucocyte function-associated antigen-1, DNAX accessory molecule-1 or tumour necrosis factor-related apoptosis-inducing ligand enhance osteoclast survival when co-cultured with activated NK cells and restore the capacity of osteoclasts to erode bone. These results suggest that interleukin-15-activated NK cells may directly affect bone erosion under physiological and pathological conditions.
(© 2015 Novo Nordisk A/S.)

Mol Pathol. 1997 Jun;50(3):132-7. (PMID: 9292147)
Endocrinology. 2013 Mar;154(3):1008-20. (PMID: 23389957)
Exp Cell Res. 1999 Feb 25;247(1):84-93. (PMID: 10047450)
J Immunol. 1999 Mar 1;162(5):2754-60. (PMID: 10072521)
J Clin Invest. 1999 May;103(9):1345-52. (PMID: 10225978)
Am J Pathol. 2005 Feb;166(2):467-76. (PMID: 15681830)
J Leukoc Biol. 1999 Nov;66(5):718-22. (PMID: 10577499)
Calcif Tissue Int. 2014 Jan;94(1):98-111. (PMID: 23912951)
Inflammation. 2014 Jun;37(3):657-69. (PMID: 24287823)
Immunology. 2014 Aug;142(4):581-93. (PMID: 24673109)
Annu Rev Immunol. 1998;16:359-93. (PMID: 9597134)
Immunity. 1999 Nov;11(5):615-23. (PMID: 10591186)
J Exp Med. 2000 Apr 3;191(7):1095-104. (PMID: 10748228)
Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):7829-34. (PMID: 10869427)
Science. 2000 Sep 1;289(5484):1504-8. (PMID: 10968780)
J Clin Invest. 2000 Dec;106(12):1481-8. (PMID: 11120755)
Nature. 2000 Nov 30;408(6812):600-5. (PMID: 11117749)
Mol Immunol. 2000 Jun;37(9):493-501. (PMID: 11163399)
J Immunol. 2001 Oct 1;167(7):3668-76. (PMID: 11564780)
Nat Rev Cancer. 2002 Nov;2(11):850-61. (PMID: 12415255)
Rheumatology (Oxford). 2003 Jul;42(7):870-8. (PMID: 12730548)
J Exp Med. 2003 Dec 15;198(12):1829-39. (PMID: 14676297)
J Immunol. 2004 Jan 1;172(1):123-9. (PMID: 14688317)
Bone. 2004 Jan;34(1):57-64. (PMID: 14751563)
J Immunol. 2004 Nov 1;173(9):5818-26. (PMID: 15494535)
Metabolism. 1976 Aug;25(8):909-55. (PMID: 181659)
Clin Endocrinol (Oxf). 1976;5 Suppl:333S-340S. (PMID: 1053251)
Endocrinology. 1988 Apr;122(4):1373-82. (PMID: 3345718)
Adv Immunol. 1989;47:187-376. (PMID: 2683611)
Biochem Biophys Res Commun. 1990 Nov 15;172(3):1035-41. (PMID: 2244889)
J Biol Chem. 1993 Aug 5;268(22):16737-45. (PMID: 8344953)
Biochim Biophys Acta. 1993 Sep 13;1178(3):259-66. (PMID: 7779165)
Science. 1997 Apr 4;276(5309):111-3. (PMID: 9082980)
J Biol Chem. 2005 Apr 22;280(16):15709-18. (PMID: 15684417)
Blood. 2006 Mar 1;107(5):2030-6. (PMID: 16304049)
Bone. 2007 Feb;40(2):323-36. (PMID: 17055352)
Arthritis Res Ther. 2006;8(4):R88. (PMID: 16684368)
J Immunol. 2007 Mar 15;178(6):3379-89. (PMID: 17339432)
Mol Cell Biochem. 2007 Jul;301(1-2):209-17. (PMID: 17286202)
Apoptosis. 2007 Sep;12(9):1623-32. (PMID: 17558561)
Immunology. 2007 Oct;122(2):291-301. (PMID: 17521371)
Blood. 2008 Aug 1;112(3):461-9. (PMID: 18650461)
Rheumatology (Oxford). 2008 Nov;47(11):1635-40. (PMID: 18786965)
Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):13028-33. (PMID: 20615964)
PLoS One. 2011;6(12):e29492. (PMID: 22242124)
PLoS One. 2012;7(2):e31959. (PMID: 22384114)
Eur J Immunol. 2013 Jan;43(1):249-57. (PMID: 22996291)
Arthritis Res Ther. 2013;15(4):216. (PMID: 23856014)

Keywords: DNAX accessory molecule-1; leucocyte function-associated antigen-1; natural killer cytotoxicity; osteoclast; tumour necrosis factor-related apoptosis-inducing ligand

0 (Antigens, Differentiation, T-Lymphocyte)
0 (CD226 antigen)
0 (Interleukin-15)
0 (Lymphocyte Function-Associated Antigen-1)
0 (TNF-Related Apoptosis-Inducing Ligand)

Date Created: 20150217 Date Completed: 20150828 Latest Revision: 20181113

20240628

PMC4479536

10.1111/imm.12449

25684021