Immunity, Inflammation and Disease (Dec 2021)

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

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

DOI
https://doi.org/10.1002/iid3.485
Journal volume & issue
Vol. 9, no. 4
pp. 1370 – 1382

Abstract

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Abstract Introduction Chronic alcohol consumption (CAC) can induce several deleterious effects on the body, including the promotion of osteoporosis; however, the immunological mechanism underlying alcohol‐induced osteoporosis is still unclear. 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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