Epigenetic remodeling by vitamin C potentiates plasma cell differentiation.
Epigenetic remodeling by vitamin C potentiates plasma cell differentiation.
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DOI：
10.7554/elife.73754
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发表时间：
2022-09-07
期刊：
影响因子：
7.7
通讯作者：
Lio, Chan-Wang Jerry
中科院分区：
文献类型：
--
作者：
Chen, Heng-Yi;Almonte-Loya, Ana;Lay, Fang-Yun;Hsu, Michael;Johnson, Eric;Gonzalez-Avalos, Edahi;Yin, Jieyun;Bruno, Richard S.;Ma, Qin;Ghoneim, Hazem E.;Wozniak, Daniel J.;Harrison, Fiona E.;Lio, Chan-Wang Jerry
抗坏血酸（维生素C）是人体必需的微量营养素。长期以来，抗坏血酸盐的严重慢性缺乏症（称为坏血病）与感染易感性增加有关。抗坏血酸如何在细胞和分子水平上影响免疫系统仍不清楚。从微量营养素分析，我们确定抗坏血酸作为一个有效的增强抗体反应，促进小鼠和人B细胞中的IL-21/STAT 3依赖性浆细胞分化。抗坏血酸的作用是独特的，因为其他抗氧化剂未能促进浆细胞分化。在早期B细胞活化过程中，抗坏血酸盐通过将细胞平衡为浆细胞谱系而不影响近端IL-21/STAT 3信号传导和总体转录组而尤其关键。作为表观遗传酶的辅因子，抗坏血酸促进TET 2/3介导的DNA修饰和Prdm 1基因座多个元件的去甲基化。DNA去甲基化增强了STAT 3在Prdm 1启动子和下游增强子处的关联，从而确保有效的基因表达和浆细胞分化。结果表明，抗体反应需要足够水平的抗坏血酸，并强调微量营养素如何调节表观遗传酶的活性来调节基因表达。我们的研究结果表明，表观遗传酶可以作为传感器来衡量代谢产物的可用性，并影响细胞命运的决定。
Ascorbate (vitamin C) is an essential micronutrient in humans. The severe chronic deficiency of ascorbate, termed scurvy, has long been associated with increased susceptibility to infections. How ascorbate affects the immune system at the cellular and molecular levels remained unclear. From a micronutrient analysis, we identified ascorbate as a potent enhancer for antibody response by facilitating the IL-21/STAT3-dependent plasma cell differentiation in mouse and human B cells. The effect of ascorbate is unique as other antioxidants failed to promote plasma cell differentiation. Ascorbate is especially critical during early B cell activation by poising the cells to plasma cell lineage without affecting the proximal IL-21/STAT3 signaling and the overall transcriptome. As a cofactor for epigenetic enzymes, ascorbate facilitates TET2/3-mediated DNA modification and demethylation of multiple elements at the Prdm1 locus. DNA demethylation augments STAT3 association at the Prdm1 promoter and a downstream enhancer, thus ensuring efficient gene expression and plasma cell differentiation. The results suggest that an adequate level of ascorbate is required for antibody response and highlight how micronutrients may regulate the activity of epigenetic enzymes to regulate gene expression. Our findings imply that epigenetic enzymes can function as sensors to gauge the availability of metabolites and influence cell fate decisions.
维生素C用于预防和治疗普通感冒。
影响因子：
15.8
作者：
Douglas, RM;Hemilä, H
通讯作者：
Hemilä, H