Immunomodulating effect of vitamin D3 derivatives on type-1 cellular immunity
Immunomodulating effect of vitamin D3 derivatives on type-1 cellular immunity
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DOI：
10.2220/biomedres.27.1
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发表时间：
2006-02-01
影响因子：
1.2
通讯作者：
Nishimura, Takashi
中科院分区：
文献类型：
--
作者：
Imazeki, Ikuo;Matsuzaki, Junko;Nishimura, Takashi
1 α，25-二羟基维生素D3[骨化三醇或1,25(OH)(2)D-3]是一种重要的活性代谢物，参与多种功能，但其体内的钙化作用限制了其治疗应用。另一方面，22-oxa-1 α，25-二羟基维生素D-3 （22-oxacalcitriol或22-oxa-1 α，25-D-3）是维生素D3 （VitD3）的低钙类似物，已被广泛用作治疗继发性甲状旁腺功能亢进症的药物。在这里，我们研究了这两种VitD3衍生物对1型免疫调节细胞如树突状细胞（DC1）、细胞毒性T细胞（Tcl）和辅助T细胞（Th1）分化的免疫调节作用。Thl条件（GM-CSF、IL-3、IL-12和ifn - γ）诱导的BALB/c小鼠骨髓源性DC （BMDC1）表达的MHC I类、11类分子和共刺激分子水平高于中性条件（GM-CSF + IL-3）诱导的BMDC0。此外，与BMDC0相比，BMDC1对诱导同种异体抗原（H-2(d)）特异性细胞毒性T淋巴细胞（CTL）具有更强的免疫刺激活性。然而，如果在BMDC1诱导培养中加入VitD3衍生物，则功能分子和1型ifn的表达受到极大抑制。此外，VitD3衍生物处理的BMDC1失去了诱导异体抗原特异性IFN γ产生Tcl的免疫刺激活性。此外，研究表明，添加VitD3衍生物抑制了产生ifn - γ的Thl细胞从卵清蛋白（OVA）特异性的幼稚Th细胞的分化，而增强了产生IL-4或il -10的Th2细胞的分化。1,25(OH)(2)D-3和22-Oxa-1 α，25-D-3之间的免疫调节活性无显著差异。因此，VitD3衍生物被证明可以抑制DC1、Tcl和Thl细胞的功能分化，而DC1、Tcl和Thl细胞在1型细胞免疫应答中起关键作用。
1 alpha,25-dihydroxyvitamin D3 [Calcitriol or 1,25(OH)(2)D-3] is an important active metabolite involved in multiple functions but its calcemic effect in vivo limits its therapeutic applications. On the other hand, 22-oxa-1 alpha,25-dibydroxyvitamin D-3 (22-oxacalcitriol or 22-Oxa-1 alpha,25-D-3), a low calcemic analog of vitamin D3 (VitD3), has been widely used as a drug for the secondary hyperparathyroidism. Here, we investigated immunomodulating effect of these two VitD3 derivatives on the differentiation of type-1 immunoregulatory cells such as dendritic cells (DC1), cytotoxic T cells (Tcl) and helper T cells (Th1). BALB/c mouse bone marrow-derived DC (BMDC1) induced by culture with Thl condition (GM-CSF, IL-3, IL-12 and IFN-gamma) expressed higher levels of MHC Class I and Class 11 molecules and co-stimulatory molecules compared with BMDC0 induced by neutral condition (GM-CSF + IL-3). In addition, BMDC1 showed stronger immunostimulating activity to induce alloantigen (H-2(d))-specific cytotoxic T lymphocytes (CTL) compared with BMDC0. However, if VitD3 derivatives were added into the culture for BMDC1 induction, the expression of functional molecules and type-1 IFNs were greatly inhibited. Moreover, VitD3 derivative-treated BMDC1 lost their immunostimulating activity to induce alloantigen-specific IFN gamma-producing Tcl. In addition, it was demonstrated that the addition of VitD3 derivatives inhibited the differentiation of IFN-gamma-producing Thl cells from ovalbumin (OVA)-specific naive Th cells, while it rather augmented the differentiation of IL-4- or IL-10-producing Th2 cells. There was no significant difference in immunomodulating activity between 1,25(OH)(2)D-3 and 22-Oxa-1 alpha,25-D-3. Thus, VitD3 derivatives are demonstrated to inhibit the functional differentiation of DC1, Tcl and Thl cells, which play a critical role in type-1 cellular immune responses.