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

Shan Feng; Suzi H Madsen; Natasja N Viller; Anita V Neutzsky-Wulff; Carsten Geisler; Lars Karlsson; Kalle Söderström

doi:10.1111/imm.12449

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

Shan Feng, Suzi H Madsen, Natasja N Viller, Anita V Neutzsky-Wulff, Carsten Geisler, Lars Karlsson, Kalle Söderström

Department of Immunology and Microbiology

18 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Immunology
Volume	145
Issue number	3
Pages (from-to)	367-79
Number of pages	13
ISSN	0019-2805
DOIs	https://doi.org/10.1111/imm.12449
Publication status	Published - 1 Jul 2015

Keywords

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

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Cite this

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

abstract = "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.",

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author = "Shan Feng and Madsen, {Suzi H} and Viller, {Natasja N} and Neutzsky-Wulff, {Anita V} and Carsten Geisler and Lars Karlsson and Kalle S{\"o}derstr{\"o}m",

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T1 - Interleukin-15-activated natural killer cells kill autologous osteoclasts via LFA-1, DNAM-1 and TRAIL, and inhibit osteoclast-mediated bone erosion in vitro

AU - Feng, Shan

AU - Madsen, Suzi H

AU - Viller, Natasja N

AU - Neutzsky-Wulff, Anita V

AU - Geisler, Carsten

AU - Karlsson, Lars

AU - Söderström, Kalle

PY - 2015/7/1

Y1 - 2015/7/1

N2 - 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.

AB - 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.

KW - Antigens, Differentiation, T-Lymphocyte

KW - Apoptosis

KW - Bone Resorption

KW - Cell Communication

KW - Cell Differentiation

KW - Cell Survival

KW - Cells, Cultured

KW - Coculture Techniques

KW - Cytotoxicity, Immunologic

KW - Flow Cytometry

KW - Humans

KW - Interleukin-15

KW - Killer Cells, Natural

KW - Lymphocyte Activation

KW - Lymphocyte Function-Associated Antigen-1

KW - Monocytes

KW - Osteoclasts

KW - TNF-Related Apoptosis-Inducing Ligand

U2 - 10.1111/imm.12449

DO - 10.1111/imm.12449

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C2 - 25684021

SN - 0019-2805

VL - 145

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EP - 379

JO - Immunology

JF - Immunology

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ER -