The active form of vitamin D (calcitriol) promotes CXCR5 expression during follicular helper T cell differentiation.

IF 4.8 4区 医学 Q2 IMMUNOLOGY
Makoto Iwata, Ayumi Takada, Rei Sakamoto, Si-Young Song, Etsuro Ito
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引用次数: 0

Abstract

Follicular helper T (Tfh) cells promote B cell differentiation and antibody production in the B cell follicles of secondary lymphoid organs. Tfh cells express their signature transcription factor BCL6, interleukin (IL)-21, and surface molecules including inducible T cell costimulator (ICOS), programmed cell death-1 (PD-1), and C-X-C motif chemokine receptor 5 (CXCR5). Migration of Tfh cells to B cell follicles largely depends on the CXCR5 expression induced by interactions with antigen-presenting dendritic cells in the T cell area. How Tfh cells acquire sufficient levels of CXCR5 expression, however, has remained unclear. Using our in vitro culture system to generate CXCR5low Tfh-like cells from naive CD4+ T cells with IL-6 in the absence of other cell types, we found that the active form of vitamin D, calcitriol, markedly enhanced CXCR5 expression after the release from persistent T cell receptor (TCR) stimulation. CH-223191, an aryl hydrocarbon receptor antagonist, further enhanced CXCR5 expression. IL-12 but not IL-4, in place of IL-6, also supported calcitriol to enhance CXCR5 expression even before the release from TCR stimulation, whereas the cell viability sharply decreased after the release. The Tfh-like cells generated with IL-6 and calcitriol exhibited chemotaxis toward C-X-C motif chemokine ligand 13 (CXCL13), expressed IL-21, and helped B cells to produce IgG antibodies in vitro more efficiently than Tfh-like cells generated without added calcitriol. Calcitriol injections into antigen-primed mice increased the proportion of CXCR5+PD-1+CD4+ cells in their lymphoid organs, and enhanced T cell entry into B cell follicles. These results suggest that calcitriol promotes CXCR5 expression in developing Tfh cells and regulates their functional differentiation.

维生素 D 的活性形式(钙三醇)可在滤泡辅助性 T 细胞分化过程中促进 CXCR5 的表达。
滤泡辅助 T(Tfh)细胞能促进次级淋巴器官 B 细胞滤泡中的 B 细胞分化和抗体生成。Tfh细胞表达其特征性转录因子BCL6、白细胞介素(IL)-21和表面分子,包括诱导性T细胞成本刺激因子、程序性细胞死亡-1(PD-1)和趋化因子受体CXCR5。Tfh 细胞向 B 细胞滤泡的迁移在很大程度上取决于与 T 细胞区的抗原递呈树突状细胞相互作用所诱导的 CXCR5 表达。然而,Tfh 细胞如何获得足够水平的 CXCR5 表达仍不清楚。利用我们的体外培养系统,在没有其他细胞类型的情况下,用 IL-6 从幼稚的 CD4+ T 细胞中生成 CXCR5 低的 Tfh 样细胞,我们发现维生素 D 的活性形式--钙三醇--在持续的 T 细胞受体(TCR)刺激释放后明显增强了 CXCR5 的表达。芳基烃受体拮抗剂 CH-223191 进一步增强了 CXCR5 的表达。IL-12 而不是 IL-4(代替 IL-6)也支持钙三醇增强 CXCR5 的表达,甚至在 TCR 刺激释放之前也是如此,而释放后细胞活力急剧下降。与不添加钙三醇的Tfh样细胞相比,用IL-6和钙三醇生成的Tfh样细胞表现出对CXCL13的趋化性,表达IL-21,并能更有效地帮助B细胞在体外产生IgG抗体。向抗原诱导的小鼠注射钙三醇可增加其淋巴器官中CXCR5+PD-1+CD4+细胞的比例,并促进T细胞进入B细胞滤泡。这些结果表明,钙三醇能促进发育中的Tfh细胞中CXCR5的表达,并调节其功能分化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
International immunology
International immunology 医学-免疫学
CiteScore
9.30
自引率
2.30%
发文量
51
审稿时长
6-12 weeks
期刊介绍: International Immunology is an online only (from Jan 2018) journal that publishes basic research and clinical studies from all areas of immunology and includes research conducted in laboratories throughout the world.
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