Alcohol consumption induces murine osteoporosis by downregulation of natural killer T‐like cell activity. Issue 4 (2nd July 2021)

• Record Type: Journal Article
• Authors: Naruo, Munehiro; Negishi, Yasuyuki; Okuda, Takahisa; Katsuyama, Midori; Okazaki, Ken; Morita, Rimpei
• Is Part Of: Immunity, inflammation and disease. Volume 9:Issue 4(2021)
• Page Start: 1370
• Page End: 1382
• Publication Date: 2021-07-02
• Subjects: alcohol‐induced osteoporosis -- dendritic cells -- macrophages -- NKT‐like cells -- osteoclast; Immunology -- Periodicals; Immunity -- Periodicals; Inflammation -- Periodicals; 616.079
• DOI: 10.1002/iid3.485
• Languages: English
• ISSNs: 2050-4527

Abstract

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. Abstract : We analyzed alcohol‐induced osteoporosis model mice, focusing on immune cells in bone. We mainly obtained three findings: (1) IL‐4‐highly producing NKT‐like cells were more abundant in bone, (2) oral alcohol consumption suppressed IL‐4 production from the NKT‐like cells, and (3) a glycolipid antigen OCH improved alcohol‐induced osteoporosis by restoring IL‐4 production.