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维生素 D 通过调节微生物群来控制结肠中 RORγt/FoxP3+ 调节性 T 细胞的数量。

Vitamin D Regulates the Microbiota to Control the Numbers of RORγt/FoxP3+ Regulatory T Cells in the Colon.

机构信息

Department of Veterinary and Biomedical Science, The Pennsylvania State University, University Park, PA, United States.

Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, PA, United States.

出版信息

Front Immunol. 2019 Jul 30;10:1772. doi: 10.3389/fimmu.2019.01772. eCollection 2019.

Abstract

The active form of vitamin D (1,25(OH)D) suppresses experimental models of inflammatory bowel disease in part by regulating the microbiota. In this study, the role of vitamin D in the regulation of microbe induced RORγt/FoxP3+ T regulatory (reg) cells in the colon was determined. Vitamin D sufficient (D+) mice had significantly higher frequencies of FoxP3+ and RORγt/FoxP3+ T reg cells in the colon compared to vitamin D deficient (D-) mice. The higher frequency of RORγt/FoxP3+ T reg cells in D+ colon correlated with higher numbers of bacteria from the XIVa and in D+ compared to D- cecum. D- mice with fewer RORγt/FoxP3+ T reg cells were significantly more susceptible to colitis than D+ mice. Transfer of the cecal bacteria from D+ or D- mice to germfree recipients phenocopied the higher numbers of RORγt/FoxP3+ cells and reduced susceptibility to colitis in D+ vs. D- recipient mice. 1,25(OH)D treatment of the D- mice beginning at 3 weeks of age did not completely recover RORγt/FoxP3+ T reg cells or the , and um XIVa numbers to D+ values. Early vitamin D status shapes the microbiota to optimize the population of colonic RORγt/FoxP3+ T reg cells important for resistance to colitis.

摘要

活性维生素 D(1,25(OH)D)通过调节微生物群部分抑制炎症性肠病的实验模型。在这项研究中,确定了维生素 D 在调节微生物诱导的结肠 RORγt/FoxP3+T 调节(reg)细胞中的作用。与维生素 D 缺乏(D-)小鼠相比,维生素 D 充足(D+)小鼠结肠中 FoxP3+和 RORγt/FoxP3+Treg 细胞的频率明显更高。D+结肠中 RORγt/FoxP3+Treg 细胞的更高频率与 XIVa 和 细菌数量的增加有关,而 D-盲肠中则相反。与 D+小鼠相比,RORγt/FoxP3+Treg 细胞较少的 D-小鼠更容易发生结肠炎。将来自 D+或 D-小鼠的盲肠细菌转移到无菌受体中,可模拟出更高数量的 RORγt/FoxP3+细胞,并降低 D+与 D-受体小鼠发生结肠炎的易感性。从 3 周龄开始用 1,25(OH)D 治疗 D-小鼠,并未完全恢复 RORγt/FoxP3+Treg 细胞或 、和 um XIVa 的数量至 D+值。早期维生素 D 状态塑造了微生物群,以优化结肠 RORγt/FoxP3+Treg 细胞的种群,这对抵抗结肠炎很重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e341/6682671/a32adb050a0a/fimmu-10-01772-g0002.jpg

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