Novel insight into the role of the vitamin D receptor in the development and function of the immune system.
Novel insight into the role of the vitamin D receptor in the development and function of the immune system.
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DOI：
10.1016/j.jsbmb.2022.106084
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发表时间：
2022-05
期刊：
影响因子：
--
通讯作者：
Cantorna MT
中科院分区：
文献类型：
--
作者：
Arora J;Wang J;Weaver V;Zhang Y;Cantorna MT
免疫细胞表达维生素D受体（VDR），因此是维生素D的靶点。可以使用Vdr抗体和蛋白质印迹法在肾脏中容易地测量Vdr蛋白。由于静息免疫细胞中VDR表达水平低，因此测量脾脏中的VDR蛋白要困难得多。为了更灵敏地测量VDR表达，将Cre酶插入VDR基因的第3外显子中，并制备不可逆表达tdTomato的报告小鼠。表达一个拷贝的VDRCre基因的小鼠被确认为VDR +/-，表达两个拷贝的小鼠被确认为VDR-/-。与VDR+/+野生型（WT）同窝仔相比，VDR +/− VDRtdTomato+的免疫细胞的初始表征显示，VDR半合子对免疫细胞频率没有影响。高tdTomato表达显示存在于骨髓（BM）和胸腺免疫细胞前体中。在外周中，单核细胞、嗜中性粒细胞和巨噬细胞具有非常高的tdTomato+（88-98%）表达，而淋巴细胞的tdTomato+范围为60-70%。组织驻留先天淋巴样细胞（ILC）1和3细胞约为60-80% tdTomoto+，而ILC 2细胞具有非常低的tdTomato表达。对VDRtdTomato+脾细胞的刺激表明，tdTomato− CD 4+和CD 8 + T细胞比它们的tdTomato+对应物增殖得更多。将T细胞分选为tdTomato+和tdTomato-，然后活化72小时。分选的tdTomato+ T细胞仅在活化后72小时后表达VDR蛋白。分选的tdTomato− T细胞比分选的tdTomato+ T细胞增殖得更多。有趣的是，tdTomato− T细胞的激活未能诱导新的tdTomato表达。数据表明，早期免疫前体表达VDR。在外周，中性粒细胞和单核细胞几乎都是tdTomato+，而一些免疫细胞（ILC 2和一些T细胞）可能永远不会表达VDR。
Immune cells express the vitamin D receptor (VDR) and are therefore vitamin D targets. The Vdr protein can be readily measured in the kidney using antibodies to the Vdr and western blot. It is much more difficult to measure Vdr protein in the spleen because of the low level of VDR expression in resting immune cells. In order to more sensitively measure VDR expression, the Cre enzyme was inserted in the 3rd exon of the VDR gene and a reporter mouse that irreversibly expresses tdTomato was made. Mice that express one copy of the VDRCre gene were confirmed to be VDR +/− and mice that express two copies were confirmed to be VDR −/−. Initial characterization of the immune cells from the VDR +/− VDRtdTomato+ compared to VDR+/+ wildtype (WT) littermates showed no effect of being hemizygous for the VDR on immune cell frequencies. High tdTomato expression was shown to be present in the bone marrow (BM) and thymus immune cell precursors. In the periphery, monocytes, neutrophils and macrophages had very high tdTomato+ (88–98%) expression while lymphocytes ranged from 60–70% tdTomato+. Tissue resident innate lymphoid cell (ILC) 1 and 3 cells were about 60–80% tdTomoto+, while ILC2 cells had very low tdTomato expression. Stimulation of VDRtdTomato+ splenocytes showed that the tdTomato− CD4+ and CD8+ T cells proliferated more than their tdTomato+ counterparts. T cells were sorted for tdTomato+ and tdTomato− and then activated for 72h. Sorted tdTomato+ T cells expressed the VDR protein only after 72h post-activation. The sorted tdTomato− T cells proliferated more than the sorted tdTomato+ T cells. Interestingly, activation of the tdTomato− T cells failed to induce new tdTomato expression. The data suggest that an early immune precursor expresses the VDR. In the periphery, neutrophils and monocytes are almost all tdTomato+, while some immune cells (ILC2 and some T cells) may never express the VDR.
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