Immunosteroid as a regulator for Th1/Th2 balance: Its possible role in autoimmune diseases
Immunosteroid as a regulator for Th1/Th2 balance: Its possible role in autoimmune diseases
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DOI：
10.1080/08916930500124122
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发表时间：
2005-08-01
期刊：
影响因子：
3.5
通讯作者：
Nishimura, T
中科院分区：
文献类型：
--
作者：
Matsuzaki, J;Tsuji, T;Nishimura, T
由Tb1和Th2细胞控制的免疫平衡对于保护宿主免受病原体入侵至关重要，而其失衡成为包括自身免疫性疾病在内的各种免疫疾病的原因。细胞因子如IL-12和IL-4是驱动初始CD4（+）T细胞分化为Th1或Th2细胞的关键因素。除细胞因子外，类固醇激素已被证明影响Th1/Th2平衡的控制和自身免疫性疾病的发病。在这里，我们将提出一个新的概念，即免疫类固醇，这是指定为免疫调节细胞产生的类固醇，也发挥了关键作用的调节Th1/Th2平衡。免疫类固醇的第一个例子是Th2依赖性产生的孕酮。Th2细胞，而不是Th1细胞表达P450SCC和20 α-HSD，并与表达3 β-HSD的小鼠成纤维细胞合作从22 R-羟基胆固醇产生孕酮。Th2依赖性产生的孕酮诱导Th1细胞凋亡，抑制Th1细胞的分化。而Th2细胞则通过代谢孕酮产生无毒的20 α-羟孕酮和20 α-HSD来逃避孕酮的毒性作用。免疫类固醇的第二个例子是树突细胞（DC）依赖性产生的1 α，25-二羟基维生素D3 [1，25（OH）（2）D]开环类固醇激素，其已被证明抑制自身免疫性疾病。我们发现，25-羟维生素D3 1 α-羟化酶，代谢25-羟维生素D3（无活性形式）为1，25（OH）（2）D在Th2-细胞因子诱导的骨髓来源的DC 2中表达，但不表达Th1-细胞因子诱导的DC 1。1，25（OH）（2）D对DC 1诱导的1型免疫有明显的抑制作用，初步证实了免疫类固醇在调节Th1/Th2平衡，影响自身免疫性疾病发病中的重要作用。因此，研究免疫类固醇在自身免疫性疾病中的调节作用将是一个重要的课题。
Immune balance controlled by Tb1 and Th2 cells is critical for the protection of host from pathogenic invasion while its imbalance becomes the cause of various immune disorders including autoimmune diseases. Cytokines, such as IL- 12 and IL4, are critical factor to drive the differentiation of naive CD4(+) T cells to Th1 or Th2 cells. In addition to cytokines, steroid hormones have been demonstrated to affect on the control of Th1/Th2 balance and the onset of autoimmune diseases. Here, we will propose a new concept that immunosteroid, which is designated as a steroid produced by immunoregulatory cells, also play a critical role for regulation of Th1/Th2 balance. First example of immunosteroid is Th2-dependently produced progesterone. Th2 cells, but not Th1 cells expressed P450scc and 20 alpha-HSD and produced progesterone from 22R-hydroxycholesterol in cooperation with 3 beta-HSD-expressing mouse fibroblasts. Th2-dependently produced progesterone induced apoptotic cell death of Th1 cells and inhibited the differentiation of Th1 cells. While Th2 cells were escaped from toxic effect of progesterone by metabolizing it to non-toxic 20 alpha-hydroxyprogesterone with 20 alpha-HSD. Second example of immunosteroid is dendritic cell (DC)-dependently produced 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)(2)D] secosteroid hormone, which has been demonstrated to inhibit autoimmune diseases. We found that 25-hydroxyvitamin D3 1 alpha-hydroxylase, which metabolize 25-hydroxyvitamin D3 (inactive form) to 1,25(OH)(2)D was expressed in Th2-cytokine induced bone marrow-derived DC2 but not Th1-cytokine induced DC1. Moreover, 1,25(OH)(2)D was significantly inhibited DC1-induced type1 immunity.Thus, we initially demonstrated the critical role of immunosteroids in the control of Th1/Th2 balance influencing on the onset of autoimmune diseases. Therefore, it will be an important issue to investigate the possible role of immunosteroids for the regulation of autoimmune diseases.