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

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/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 a-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.