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

Immun Inflamm Dis. 2021 Dec;9(4):1370-1382. doi: 10.1002/iid3.485. Epub 2021 Jul 2.

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.

Keywords: NKT-like cells; alcohol-induced osteoporosis; dendritic cells; macrophages; osteoclast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Drinking / adverse effects
  • Animals
  • Down-Regulation
  • Killer Cells, Natural*
  • Mice
  • Mice, Inbred C57BL
  • Osteoporosis* / chemically induced