Alcohol consumption induces murine osteoporosis by downregulation of natural killer T-like cell activity.
Alcohol consumption induces murine osteoporosis by downregulation of natural killer T-like cell activity.
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DOI：
10.1002/iid3.485
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发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
Morita R
中科院分区：
文献类型：
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作者：
Naruo M;Negishi Y;Okuda T;Katsuyama M;Okazaki K;Morita R
慢性饮酒（CAC）可对身体产生多种有害影响，包括促进骨质疏松症;然而，酒精诱导骨质疏松症的免疫学机制仍不清楚。我们将酒精作为实验性CAC模型给予小鼠4周，并分析了骨和位于骨附近的免疫细胞。已知IL-4是破骨细胞生成的抑制因子，我们发现自然杀伤T（NKT）样细胞（NK1.1阳性、CD 3阳性和α-半乳糖神经酰胺负载的CD 1d四聚体阴性）比CD 4 + T和自然杀伤（NK）细胞更有效地产生IL-4。饮酒促进了骨密度的显著降低，并上调了活化T细胞核因子1和NF-κB配体受体激活剂的表达。同时，我们证实饮酒抑制了抗原呈递细胞（APC）和NKT样细胞的活性，导致IL-4分泌减少。此外，这些有害的影响，酒精消费减少了同时治疗与糖脂抗原OCH。我们的研究结果表明，先天免疫细胞，APC和NKT样细胞的失活可能是酒精诱导的骨质疏松症的关键，并为预防骨质疏松症提供了一种新的治疗方法。我们分析了酒精诱导的骨质疏松症模型小鼠，重点是骨骼中的免疫细胞。我们主要获得了三个发现：（1）IL-4高产NKT-样细胞在骨中更丰富，（2）口服酒精消耗抑制了NKT-样细胞的IL-4产生，（3）糖脂抗原OCH通过恢复IL-4的产生来改善酒精诱导的骨质疏松症。
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. 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. 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. 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. 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.
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影响因子：
2.8
作者：
Callaci, John J.;Himes, Ryan;Roper, Phillip
通讯作者：
Roper, Phillip
DOI：
10.1111/acer.13000
发表时间：
2016-04
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Gaddini GW;Turner RT;Grant KA;Iwaniec UT
通讯作者：
Iwaniec UT
DOI：
10.4049/jimmunol.1700214
发表时间：
2017-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Clancy-Thompson E;Chen GZ;Tyler PM;Servos MM;Barisa M;Brennan PJ;Ploegh HL;Dougan SK
通讯作者：
Dougan SK
DOI：
10.1007/978-1-62703-989-5_11
发表时间：
2014-01-01
期刊：
SKELETAL DEVELOPMENT AND REPAIR: METHODS AND PROTOCOLS
影响因子：
--
作者：
Kawamoto, Tadafumi;Kawamoto, Komei
通讯作者：
Kawamoto, Komei
影响因子：
30.5
作者：
通讯作者：
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