Interleukin-15-activated natural killer cells kill autologous osteoclasts via LFA-1, DNAM-1 and TRAIL, and inhibit osteoclast-mediated bone erosion in vitro
| Autor: | Natasja N. Viller, Anita V. Neutzsky-Wulff, Shan Feng, Lars Karlsson, Suzi H. Madsen, Carsten Geisler, Kalle Söderström |
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| Rok vydání: | 2014 |
| Předmět: |
musculoskeletal diseases
Antigens Differentiation T-Lymphocyte Cytotoxicity Immunologic Cell Survival Cellular differentiation Immunology Osteoclasts Apoptosis Cell Communication Biology Lymphocyte Activation Bone resorption Monocytes TNF-Related Apoptosis-Inducing Ligand Interleukin 21 Osteoclast medicine Immunology and Allergy Humans Lymphocyte function-associated antigen 1 Bone Resorption Cells Cultured Interleukin-15 Cell Differentiation Original Articles Flow Cytometry Coculture Techniques Lymphocyte Function-Associated Antigen-1 Cell biology Killer Cells Natural medicine.anatomical_structure Interleukin 15 Interleukin 12 Bone marrow |
| Zdroj: | Immunology. 145(3) |
| ISSN: | 1365-2567 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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