1,25-Dihydroxyvitamin D3 and IL-2 combine to inhibit T cell production of inflammatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FoxP3.
1,25-Dihydroxyvitamin D3 and IL-2 combine to inhibit T cell production of inflammatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FoxP3.
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1,25-二羟基维生素D3和IL-2结合抑制炎性细胞因子的T细胞产生，并促进表达CTLA-4和FOXP3的调节性T细胞的发育。
DOI：
10.4049/jimmunol.0803217
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发表时间：
2009-11-01
期刊：
影响因子：
--
通讯作者：
Sansom DM
中科院分区：
文献类型：
--
作者：
Jeffery LE;Burke F;Mura M;Zheng Y;Qureshi OS;Hewison M;Walker LS;Lammas DA;Raza K;Sansom DM
维生素D的活性形式，1，25-二羟基维生素D3（1，25（OH）2D 3）具有有效的免疫调节特性，促进了其在预防和治疗感染性疾病和自身免疫性疾病中的潜在用途。多种免疫细胞，包括巨噬细胞、树突状细胞和活化的T细胞，表达细胞内维生素D受体（VDR）并对1，25（OH）2D 3有反应。尽管如此，1，25（OH）2D 3如何调节适应性免疫仍不清楚，可能涉及对T细胞增殖和功能的直接和间接影响。为了进一步阐明这个问题，我们评估了1，25（OH）2D 3对人CD 4 + CD 25 − T细胞的影响。我们观察到，在1，25（OH）2D 3存在下刺激CD 4 + CD 25 − T细胞可抑制促炎细胞因子（包括IFN- γ、IL-17和IL-21）的产生，但对T细胞分裂没有实质性影响。与其对炎性细胞因子的抑制作用相反，1，25（OH）2D 3刺激高水平的CTLA-4以及FoxP 3的表达，后者需要IL-2的存在。经1，25（OH）_2D_3处理的T细胞能抑制正常反应性T细胞的增殖，表明其具有适应性T细胞的特征。我们的研究结果表明，1，25（OH）2D 3和IL-2对活化的T细胞具有直接的协同作用，作为有效的抗炎剂和适应性T细胞的生理诱导剂。
The active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has potent immunomodulatory properties that have promoted its potential use in the prevention and treatment of infectious disease and autoimmune conditions. A variety of immune cells, including macrophages, dendritic cells and activated T cells express the intracellular vitamin D receptor (VDR) and are responsive to 1,25(OH)2D3. Despite this, how 1,25(OH)2D3 regulates adaptive immunity remains unclear, and may involve both direct and indirect effects on the proliferation and function of T cells. To further clarify this issue we have assessed the effects of 1,25(OH)2D3 on human CD4+ CD25− T cells. We observed that stimulation of CD4+ CD25− T cells in the presence of 1,25(OH)2D3 inhibited production of pro-inflammatory cytokines including IFN- γ, IL-17 and IL-21 but did not substantially affect T cell division. In contrast to its inhibitory effects on inflammatory cytokines, 1,25(OH)2D3 stimulated expression of high levels of CTLA-4 as well as FoxP3, the latter requiring the presence of IL-2. T cells treated with 1,25(OH)2D3 could suppress proliferation of normally responsive T cells indicating that they possessed characteristics of adaptive Tregs. Our results suggest that 1,25(OH)2D3 and IL-2 have direct synergistic effects on activated T cells, acting as potent anti-inflammatory agents and physiologic inducers of adaptive Tregs.
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影响因子：
15.3
作者：
Apostolou, I;von Boehmer, H
通讯作者：
von Boehmer, H
DOI：
10.1111/j.1749-6632.2003.tb06057.x
发表时间：
2003-01-01
期刊：
IMMUNE MECHANISMS AND DISEASE
影响因子：
--
作者：
Adorini, L
通讯作者：
Adorini, L
影响因子：
4.4
作者：
DiPaolo, Richard J.;Brinster, Carine;Shevach, Ethan M.
通讯作者：
Shevach, Ethan M.
影响因子：
4.4
作者：
Boonstra, A;Barrat, FJ;O'Garra, A
通讯作者：
O'Garra, A
影响因子：
30.5
作者：
Denning, Timothy L.;Wang, Yi-Chong;Pulendran, Bali
通讯作者：
Pulendran, Bali