Immunoporosis: A New Role for Invariant Natural Killer T (NKT) Cells Through Overexpression of Nuclear Factor-κB Ligand (RANKL)

Tilkeridis, Konstantinos; Kiziridis, Georgios; Ververidis, Athanasios; Papoutselis, Menelaos; Kotsianidis, Ιoannis; Kitsikidou, Gesthimani; Tousiaki, Natalia-Efthalia; Drosos, Georgios I.; Kapetanou, Artemis; Rechova, Katerina Vlastimil; Kazakos, Konstantinos; Spanoudakis, Emmanouil

doi:10.12659/msm.912119

Cited by 15 publications

(13 citation statements)

References 30 publications

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“…CD4+ T cells increase osteoclastogenesis by affecting RANKL/OPG ratio [ 60 ] and RANKL secreted by B cells increases osteoclastogenesis [ 61 ]. Additionally, Tregs [ 62 ] and NKT [ 63 ] mediate bone loss via RANKL. B cells are important for the development of osteoblasts and osteoclasts [ 64 ].…”

Section: Immuno-oncology and Bonementioning

confidence: 99%

Osteoimmuno-Oncology: Therapeutic Opportunities for Targeting Immune Cells in Bone Metastasis

Kähkönen¹,

Halleen²,

Bernoulli

2021

Cells

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Immunotherapies provide a potential treatment option for currently incurable bone metastases. Bone marrow is an important secondary lymphoid organ with a unique immune contexture. Even at non-disease state immune cells and bone cells interact with each other, bone cells supporting the development of immune cells and immune cells regulating bone turnover. In cancer, tumor cells interfere with this homeostatic process starting from formation of pre-metastatic niche and later supporting growth of bone metastases. In this review, we introduce a novel concept osteoimmuno-oncology (OIO), which refers to interactions between bone, immune and tumor cells in bone metastatic microenvironment. We also discuss therapeutic opportunities of targeting immune cells in bone metastases, and associated efficacy and safety concerns.

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Section: Immuno-oncology and Bonementioning

confidence: 99%

Osteoimmuno-Oncology: Therapeutic Opportunities for Targeting Immune Cells in Bone Metastasis

Kähkönen¹,

Halleen²,

Bernoulli

2021

Cells

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“…Moreover, the LAMP-2 knock-out mice did not show a bone phenotype, thus suggesting properly functioning osteoclasts. To come up with an explanation for the differences between the in vivo and in vitro findings we assume that other cell types such as osteocytes and T-cells, from which is known that they have the capacity to express RANKL, facilitated osteoclastogenesis [ 41 , 42 , 43 , 44 ]. In this way the inability of osteoblasts to express RANKL might be compensated by other cell types.…”

Section: Discussionmentioning

confidence: 99%

LAMP-2 Is Involved in Surface Expression of RANKL of Osteoblasts In Vitro

Jansen

Tigchelaar-Gutter

Hogervorst

et al. 2020

IJMS

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Lysosome associated membrane proteins (LAMPs) are involved in several processes, among which is fusion of lysosomes with phagosomes. For the formation of multinucleated osteoclasts, the interaction between receptor activator of nuclear kappa β (RANK) and its ligand RANKL is essential. Osteoclast precursors express RANK on their membrane and RANKL is expressed by cells of the osteoblast lineage. Recently it has been suggested that the transport of RANKL to the plasma membrane is mediated by lysosomal organelles. We wondered whether LAMP-2 might play a role in transportation of RANKL to the plasma membrane of osteoblasts. To elucidate the possible function of LAMP-2 herein and in the formation of osteoclasts, we analyzed these processes in vivo and in vitro using LAMP-2-deficient mice. We found that, in the presence of macrophage colony stimulating factor (M-CSF) and RANKL, active osteoclasts were formed using bone marrow cells from calvaria and long bone mouse bone marrow. Surprisingly, an almost complete absence of osteoclast formation was found when osteoclast precursors were co-cultured with LAMP-2 deficient osteoblasts. Fluorescence-activated cell sorting FACS analysis revealed that plasma membrane-bound RANKL was strongly decreased on LAMP-2 deficient osteoblasts. These results suggest that osteoblastic LAMP-2 is required for osteoblast-induced osteoclast formation in vitro.

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“…It is not known whether there are specific differences in the cell types populating PBMCs of nonosteoporotic individuals and osteopenia and osteoporosis patients. However, T lymphocytes [23, 24] and natural killer cells [25] have been reported to contribute to osteoporosis by their activation and production of osteoclastogenic cytokines, but the observation that various T cell subtypes can exhibit either osteoclastogenic, e.g., Thy 17, or antiosteoclastogenic activity, e.g., Thy1 [26], suggests that there is a balance between pro- and antiosteoclastic activity in T cell subtypes. Whilst, little, if anything, is known about any possible role of TMEM64 in these processes in T lymphocytes, the presence of annexin A1, on the other hand, has been widely associated with the resolution of inflammatory disorders [12, 13, 27].…”

Section: Discussionmentioning

confidence: 99%

Altered Levels of mRNAs for Calcium-Binding/Associated Proteins, Annexin A1, S100A4, and TMEM64, in Peripheral Blood Mononuclear Cells Are Associated with Osteoporosis

et al. 2019

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Background Osteoporosis is the most common metabolic bone disease in the world. Since osteoporosis is clinically symptomless until the first fracture occurs, early diagnosis is critical. Calcium, along with calcium-binding and calcium-associated proteins, plays an important role in homeostasis, maintaining healthy bone metabolism. This study is aimed at investigating the level of calcium-binding/associated proteins, annexin A1, S100A4, and TMEM64, in peripheral blood mononuclear cells associated with osteoporosis and its clinical significance. Methods The levels of mRNAs of annexin A1, S100A4, and TMEM64 in human peripheral blood mononuclear cells were evaluated among 48 osteopenia and 23 osteoporosis patients compared to 17 nonosteoporotic controls. Total RNAs were isolated from clinical samples, and quantitation of mRNA levels was performed using real-time quantitative PCR. Results The levels of mRNAs for calcium-binding proteins, annexin A1 and S100A4, and calcium-associated protein, TMEM64, in human peripheral blood mononuclear cells were significantly reduced in osteopenia and osteoporosis patients compared with nonosteoporotic controls (one-way ANOVA, P < 0.0001, P = 0.039, and P = 0.0195, respectively). Annexin A1 and TMEM64 mRNAs were also significantly reduced in female osteoporosis patients over the age of 50 years compared to nonosteoporotic controls (one-way ANOVA, P = 0.004 and P = 0.0037, respectively). ROC analysis showed that the reduction in the level of mRNA for annexin A1, S100A4, or TMEM64 in the patients' peripheral blood mononuclear cells has a good diagnostic value for osteoporosis. Conclusions The results show for the first time that calcium-binding/associated proteins, annexin A1 and TMEM64, could be future diagnostic biomarkers for osteoporosis.

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Immunoporosis: A New Role for Invariant Natural Killer T (NKT) Cells Through Overexpression of Nuclear Factor-κB Ligand (RANKL)

Cited by 15 publications

References 30 publications

Osteoimmuno-Oncology: Therapeutic Opportunities for Targeting Immune Cells in Bone Metastasis

Osteoimmuno-Oncology: Therapeutic Opportunities for Targeting Immune Cells in Bone Metastasis

LAMP-2 Is Involved in Surface Expression of RANKL of Osteoblasts In Vitro

Altered Levels of mRNAs for Calcium-Binding/Associated Proteins, Annexin A1, S100A4, and TMEM64, in Peripheral Blood Mononuclear Cells Are Associated with Osteoporosis

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