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23 March 2019 : Clinical Research  

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

Konstantinos Tilkeridis1ADE, Georgios Kiziridis1BDEFG*, Athanasios Ververidis1A, Menelaos Papoutselis2B, Ioannis Kotsianidis2A, Gesthimani Kitsikidou1A, Natalia-Efthalia Tousiaki2D, Georgios Drosos1AD, Artemis Kapetanou1B, Katerina Vlastimil Rechova3D, Konstantinos Kazakos1A, Emmanouil Spanoudakis2ACDEF

DOI: 10.12659/MSM.912119

Med Sci Monit 2019; 25:2151-2158


BACKGROUND: Osteoporosis affects millions of postmenopausal women worldwide. Invariant natural killer T cells (iNKT) are important cells for bone homeostasis. The sim of this study was to investigate the contribution of invariant natural killer T cells (iNKT) in the increased receptor activator of the nuclear factor-κB ligand (RANKL) pool and bone resorption, a characteristic of patients with osteoporosis.

MATERIAL AND METHODS: Whole blood was collected from 79 female patients. The dual energy x-absorptiometry scan was performed in all patients, and the T-score was calculated in order to classify our patients according to the World Human Organization (WHO) criteria for diagnosis and classification of osteoporosis. Eleven patients had a T-score <–1.0 and were encompassed in our normal donors (ND) group, 46 patients had a T-score between –1 and –2.5 and were included in the osteopenia group, while 22 patients had a T-score > –2.5 and were included in the osteoporosis group. We performed α-galactosylceramide activation of iNKT cells in vitro. Surface RANKL expression was detected by multicolor flow cytometry in naive and activated lymphocytes. Beta-Crosslaps (β-CTx) levels were measured in whole blood plasma by ELISA (enzyme-linked immunosorbent assay).

RESULTS: Although iNKT cells were not clonally expanded in patients with osteoporosis, iNKT cells from osteoporotic patients overexpressed RANKL compared to ND and osteopenic patients. This is a distinctive feature of iNKT cells and is not seen in conventional T-lymphocytes. RANKL expression in iNKT cells was not related to β-CTx levels in the blood. Finally, iNKT cell activation by the prototypal glycolipid ligand α-galactosylceramide increased by 8 times their RANKL expression.

CONCLUSIONS: In patients with osteoporosis, iNKT cells specifically overexpress RANKL, a cytokine that regulates osteoclast activity. It seems that iNKT cells have a long-standing effect of on the bone physiology, which plays an important role in the bone loss of patients with osteoporosis.

Keywords: Glycolipids, Natural Killer T-Cells, Osteoporosis, RANK Ligand, Aged, Aged, 80 and over, Cytokines, Flow Cytometry, Lymphocyte Activation, Middle Aged

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Science Editor, Medical Science Monitor, International Scientific Information, Inc., Melville, NY, USA

DOI: 10.12659/MSM.942672

Med Sci Monit 2023; 29:e942672


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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750