Alcohol consumption induces murine osteoporosis by downregulation of natural killer T-like cell activity

饮酒通过下调自然杀伤性T细胞活性诱发小鼠骨质疏松症

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作者:Munehiro Naruo, Yasuyuki Negishi, Takahisa Okuda, Midori Katsuyama, Ken Okazaki, Rimpei Morita

Conclusions

Our results indicate that the inactivation of innate immune cells, APCs, and NKT-like cells are likely to be crucial for alcohol-induced osteoporosis and provide a new therapeutic approach for preventing osteoporosis.

Methods

We administered alcohol to mice for 4 weeks as the experimental CAC model and analyzed the bone and immune cells that are located in the vicinity of a bone.

Results

IL-4 is known to be a suppressive factor for osteoclastogenesis, and we found that natural killer T (NKT)-like cells, which showed NK1.1-positive, CD3-positive, and α-galactosylceramide-loaded CD1d tetramer-negative, produced IL-4 more effectively than CD4+ T and natural killer (NK) cells. The alcohol consumption facilitated a significant decrease of bone mineral density with the upregulation of nuclear factor of activated T cells 1 and receptor activator of NF-κB ligand expression. Meanwhile, we confirmed that alcohol consumption suppressed the activity of antigen-presenting cells (APCs) and NKT-like cells, leading to decreased IL-4 secretion. Moreover, these harmful effects of alcohol consumption were reduced by simultaneous treatment with a glycolipid antigen OCH. Conclusions: Our results indicate that the inactivation of innate immune cells, APCs, and NKT-like cells are likely to be crucial for alcohol-induced osteoporosis and provide a new therapeutic approach for preventing osteoporosis.

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