Vitamin D receptor upregulation in alloreactive human T cells
Vitamin D receptor upregulation in alloreactive human T cells
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DOI：
10.1016/j.humimm.2012.04.019
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发表时间：
2012-07-01
期刊：
影响因子：
2.7
通讯作者：
Komanduri, Krishna V.
中科院分区：
文献类型：
--
作者：
Joseph, Richard W.;Bayraktar, Ulas D.;Komanduri, Krishna V.
维生素D缺乏症与以炎症为特征的疾病有不利关系。接受异基因干细胞移植（SCT）的患者中维生素D缺乏症的高发病率和维生素D缺乏症在影响移植物抗宿主病中的潜在作用相结合，使我们进一步表征同种异体反应性T细胞上VDR的表达。我们假设维生素D受体表达可能直接调节同种异体反应性T细胞反应。为了克服在大量细胞群体中测量VDR的现有限制，我们开发了流式细胞术测定来测量人T细胞中的细胞质VDR。刺激后，VDR表达极早，并表现出持续上调与慢性刺激。VDR表达还与细胞因子的产生、增殖和ERK 1/2磷酸化相关。此外，VDR表现出成熟阶段特异性的表达模式，在已知介导GVHD的细胞、幼稚和早期记忆T细胞上表达最多。同种异体反应性T细胞上调VDR，而非反应性T细胞没有。最后，体外补充维生素D足以显著降低同种异体反应性T细胞反应。这些数据表明，维生素D对T细胞的影响可能是重要的，在减少移植物抗宿主病（GVHD）的异基因干细胞移植设置。(c)2012年美国组织相容性和免疫遗传学学会。爱思唯尔公司出版All rights reserved.
Vitamin D deficiency is adversely associated with diseases characterized by inflammation. The combination of the high incidence of vitamin D deficiency in patients undergoing allogeneic stem cell transplants (SCT) and the potential role of vitamin D deficiency in influencing graft-versus-host disease led us to further characterize the expression of VDR on alloreactive T cells. We hypothesized that vitamin D receptor expression may directly regulate alloreactive T cell responses. To overcome existing limitations in measuring VDR in bulk cellular populations, we developed a flow cytometric assay to measure cytoplasmic VDR in human T cells. Upon stimulation, VDR was expressed extremely early and exhibited sustained upregulation with chronic stimulation. VDR expression was also coupled to cytokine production, proliferation, and ERK1/2 phosphorylation. In addition, VDR exhibited a maturation stage-specific pattern of expression, with greatest expression on cells known to mediate GVHD, naive and early memory T cells. Alloreactive T cells upregulated VDR, whereas the nonreactive T cells did not. Finally, repletion of vitamin D in vitro was sufficient to significantly reduce alloreactive T cell responses. These data suggest that vitamin D effects on T cells may be important in reducing graft versus host disease (GVHD) in the allogeneic stem cell transplant setting. (c) 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.