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

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 t...

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Main Authors: Munehiro Naruo, Yasuyuki Negishi, Takahisa Okuda, Midori Katsuyama, Ken Okazaki, Rimpei Morita
Format: Article
Language:English
Published: Wiley 2021-12-01
Series:Immunity, Inflammation and Disease
Subjects:
Online Access:https://doi.org/10.1002/iid3.485
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author Munehiro Naruo
Yasuyuki Negishi
Takahisa Okuda
Midori Katsuyama
Ken Okazaki
Rimpei Morita
author_facet Munehiro Naruo
Yasuyuki Negishi
Takahisa Okuda
Midori Katsuyama
Ken Okazaki
Rimpei Morita
author_sort Munehiro Naruo
collection DOAJ
description 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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spelling doaj-art-2f546ec108a74e0a9eeeb219efd7d8fe2025-08-20T03:58:37ZengWileyImmunity, Inflammation and Disease2050-45272021-12-01941370138210.1002/iid3.485Alcohol consumption induces murine osteoporosis by downregulation of natural killer T‐like cell activityMunehiro Naruo0Yasuyuki Negishi1Takahisa Okuda2Midori Katsuyama3Ken Okazaki4Rimpei Morita5Department of Microbiology and Immunology Nippon Medical School Tokyo JapanDepartment of Microbiology and Immunology Nippon Medical School Tokyo JapanDepartment of Legal Medicine Nihon University School of Medicine Tokyo JapanDepartment of Legal Medicine Graduate School of Medical and Dental Sciences Kagoshima University Kagoshima JapanDepartment of Orthopaedic Surgery Tokyo Women's Medical University Tokyo JapanDepartment of Microbiology and Immunology Nippon Medical School Tokyo JapanAbstract 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.https://doi.org/10.1002/iid3.485alcohol‐induced osteoporosisdendritic cellsmacrophagesNKT‐like cellsosteoclast
spellingShingle Munehiro Naruo
Yasuyuki Negishi
Takahisa Okuda
Midori Katsuyama
Ken Okazaki
Rimpei Morita
Alcohol consumption induces murine osteoporosis by downregulation of natural killer T‐like cell activity
Immunity, Inflammation and Disease
alcohol‐induced osteoporosis
dendritic cells
macrophages
NKT‐like cells
osteoclast
title Alcohol consumption induces murine osteoporosis by downregulation of natural killer T‐like cell activity
title_full Alcohol consumption induces murine osteoporosis by downregulation of natural killer T‐like cell activity
title_fullStr Alcohol consumption induces murine osteoporosis by downregulation of natural killer T‐like cell activity
title_full_unstemmed Alcohol consumption induces murine osteoporosis by downregulation of natural killer T‐like cell activity
title_short Alcohol consumption induces murine osteoporosis by downregulation of natural killer T‐like cell activity
title_sort alcohol consumption induces murine osteoporosis by downregulation of natural killer t like cell activity
topic alcohol‐induced osteoporosis
dendritic cells
macrophages
NKT‐like cells
osteoclast
url https://doi.org/10.1002/iid3.485
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AT takahisaokuda alcoholconsumptioninducesmurineosteoporosisbydownregulationofnaturalkillertlikecellactivity
AT midorikatsuyama alcoholconsumptioninducesmurineosteoporosisbydownregulationofnaturalkillertlikecellactivity
AT kenokazaki alcoholconsumptioninducesmurineosteoporosisbydownregulationofnaturalkillertlikecellactivity
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