Activated T lymphocytes suppress osteoclastogenesis by diverting early monocyte/macrophage progenitor lineage commitment towards dendritic cell differentiation through down-regulation of receptor activator of nuclear factor-kappaB and c-Fos

Znanstveni rad - Izvorni znanstveni rad

• Autor: Danka Grčević
• Autor: Ivan Krešimir Lukić
• Autor: Nataša Kovačić
• Autor: Sanja Ivčević
• Autor: Vedran Katavić
• Autor: Ana Marušić
• Autorova ustanova: Sveučilište u Zagrebu; Medicinski fakultet
• Znanstveno / umjetničko područje, polje i grana: BIOMEDICINA I ZDRAVSTVO; Temeljne medicinske znanosti

Sažetak (engleski)

Activated T lymphocytes either stimulate or inhibit osteoclastogenesis from haematopoietic progenitors in different experimental models. To address this controversy, we used several modes of T lymphocyte activation in osteoclast differentiation--mitogen-pulse, anti-CD3/CD28 stimulation and in vivo and in vitro alloactivation. Osteoclast-like cells were generated from non-adherent immature haematopoietic monocyte/macrophage progenitors in murine bone-marrow in the presence of receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) and monocyte-macrophage colony-stimulating factor (M-CSF). All modes of in vivo and in vitro T lymphocyte activation and both CD4(+) and CD8(+) subpopulations produced similar inhibitory effects on osteoclastogenesis paralleled by enhanced dendritic cell (DC) differentiation. Osteoclast-inhibitory effect was associated with T lymphocyte activation and not proliferation, and could be replaced by their culture supernatants. The stage of osteoclast differentiation was crucial for the inhibitory action of activated T lymphocytes on osteoclastogenesis, because the suppressive effect was visible only on early osteoclast progenitors but not on committed osteoclasts. Inhibition was associated specifically with increased granulocyte-macrophage colony-stimulating factor (GM-CSF) expression by the mechanism of progenitor commitment toward lineages other than osteoclast because activated T lymphocytes down-regulated RANK, CD115, c-Fos and calcitonin receptor expression, and increased differentiation towards CD11c-positive DC. An activated T lymphocyte inhibitory role in osteoclastogenesis, confirmed in vitro and in vivo, mediated through GM-CSF release, may be used to counteract activated bone resorption mediated by T lymphocyte-derived cytokines in inflammatory and immune disorders. We also demonstrated the importance of alloactivation in osteoclast differentiation and the ability of cyclosporin A to abrogate T lymphocyte inhibition of osteoclastogenesis, thereby confirming the functional link between alloreaction and bone metabolism.

• Ključne riječi (engleski): Dendritic Cells - cytology; Lymphocyte Activation - physiology; Osteoclasts - cytology - drug effects - metabolism; T-Lymphocytes - immunology; Animals; Cell Differentiation - drug effects - immunology - physiology; Cyclosporine - pharmacology; Down-Regulation - immunology; Female; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism; Immunosuppressive Agents - pharmacology; Lymphocyte Culture Test, Mixed; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Proto-Oncogene Proteins c-fos - metabolism; RANK Ligand - metabolism; Receptor Activator of Nuclear Factor-kappa B - metabolism; Receptor, Macrophage Colony-Stimulating Factor - metabolism; Receptors, Calcitonin - metabolism
• Jezik: engleski
• Vrsta publikacije: Znanstveni rad - Izvorni znanstveni rad
• Status objave: Objavljen
• Vrsta recenzije: Recenziran
• Verzija publikacije: Završna verzija rukopisa prihvaćena za objavljivanje (postprint)
• Naslov časopisa: Clinical and experimental immunology
• Brojčani podaci: vol. 146, br. 1, str. 146-158
• p-ISSN: 0009-9104
• DOI: https://doi.org/10.1111/j.1365-2249.2006.03181.x
• URN:NBN: urn:nbn:hr:105:188126
• Datum objave publikacije: 2006-10
• URL dokumenta: https://doi.org/10.1111/j.1365-2249.2006.03181.x|
• Vrsta resursa: Tekst
• Prava pristupa: Otvoreni pristup
• Datum i vrijeme pohrane: 2024-03-28 09:40:41