Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University, Atlanta, GA, USA.
Department of Pediatrics, Emory University, Atlanta, GA, USA.
Immunity. 2018 Dec 18;49(6):1116-1131.e7. doi: 10.1016/j.immuni.2018.10.013. Epub 2018 Nov 13.
Nutritional supplementation with probiotics can prevent pathologic bone loss. Here we examined the impact of supplementation with Lactobacillus rhamnosus GG (LGG) on bone homeostasis in eugonadic young mice. Micro-computed tomography revealed that LGG increased trabecular bone volume in mice, which was due to increased bone formation. Butyrate produced in the gut following LGG ingestion, or butyrate fed directly to germ-free mice, induced the expansion of intestinal and bone marrow (BM) regulatory T (Treg) cells. Interaction of BM CD8 T cells with Treg cells resulted in increased secretion of Wnt10b, a bone anabolic Wnt ligand. Mechanistically, Treg cells promoted the assembly of a NFAT1-SMAD3 transcription complex in CD8 cells, which drove expression of Wnt10b. Reducing Treg cell numbers, or reconstitution of TCRβ mice with CD8 T cells from Wnt10b mice, prevented butyrate-induced bone formation and bone mass acquisition. Thus, butyrate concentrations regulate bone anabolism via Treg cell-mediated regulation of CD8 T cell Wnt10b production.
益生菌营养补充可以预防病理性骨质流失。在这里，我们研究了补充鼠李糖乳杆菌 GG（LGG）对生育正常的年轻小鼠骨稳态的影响。微计算机断层扫描显示，LGG 增加了小鼠的小梁骨体积，这是由于骨形成增加所致。LGG 摄入后在肠道中产生的丁酸盐，或直接给予无菌小鼠的丁酸盐，诱导肠道和骨髓（BM）调节性 T（Treg）细胞的扩张。BM CD8 T 细胞与 Treg 细胞的相互作用导致骨形成 Wnt 配体 Wnt10b 的分泌增加。从机制上讲，Treg 细胞促进了 NFAT1-SMAD3 转录复合物在 CD8 细胞中的组装，从而驱动了 Wnt10b 的表达。减少 Treg 细胞数量，或用来自 Wnt10b 小鼠的 CD8 T 细胞重建 TCRβ 小鼠，可预防丁酸盐诱导的骨形成和骨量增加。因此，丁酸盐浓度通过 Treg 细胞介导的 CD8 T 细胞 Wnt10b 产生来调节骨合成代谢。
