Suppression by CD4+CD25+ regulatory T cells is dependent on expression of heme oxygenase-1 in antigen-presenting cells
Suppression by CD4+CD25+ regulatory T cells is dependent on expression of heme oxygenase-1 in antigen-presenting cells
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DOI：
10.2353/ajpath.2008.070963
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发表时间：
2008-07-01
影响因子：
6
通讯作者：
Kapturczakt, Matthias H.
中科院分区：
文献类型：
--
作者：
George, James F.;Braun, Andrea;Kapturczakt, Matthias H.
血红素氧合酶-1(HO-1)被认为是一种细胞保护蛋白，可减轻炎性细胞损伤，并有助于保护同种异体移植物免受急、慢性排斥反应，在先天性免疫反应和获得性免疫反应中具有重要作用。HO-1基因缺陷的小鼠表现出免疫调节缺陷，表现为促炎表型。我们检查了调节性T细胞(Treg)功能受损是否与HO-1(-/-)小鼠观察到的免疫调节缺陷有关。与HO-1(+/+)小鼠相比，HO-1(-/-)小鼠体内表达Foxp3的CD25(+)细胞比例明显高于HO-1(-/+)小鼠，并且HO-1(-/-)Treg细胞在体外抑制HO-1(+/+)或HO-1(-/-)小鼠的效应T细胞增殖方面至少与HO-1(+/+)Treg细胞一样有效。然而，抗原提呈细胞中HO-1的缺失取消了Treg细胞对效应性T细胞的抑制活性。这些发现表明，抗原提呈细胞中的HO-1活性对于Treg介导的抑制是重要的，这为HO-1(-/-)小鼠免疫调节的明显缺陷提供了解释。
Heme oxygenase-1 (HO-1) has been viewed as a cytoprotective protein, ameliorating the effects of inflammatory cellular damage, and as beneficial in allograft protection from acute and chronic rejection, suggesting important functions in both innate and adaptive immune responses. Mice deficient in HO-1 exhibit defective immune regulation characterized by a proinflammatory phenotype. We examined if impaired regulatory T cell (Treg) function contributes to the immunoregulatory defects observed in HO-1(-/-) mice. HO-1(-/-) mice exhibited a significantly higher proportion of Foxp3-expressing cells among total CD4(+) and CD4(+)CD25(+) cells in comparison to HO-1(+/+) mice, and HO-1(-/-) Treg cells were at least as effective as HO-1(+/+) Treg cells in suppressing proliferation of effector T cells in vitro from either HO-1(+/+) or HO-1(-/-) mice. However, the absence of HO-1 in antigen-presenting cells abolished the suppressive activity of Treg cells on effector T cells. These findings demonstrate that HO-1 activity in antigen-presenting cells is important for Treg-mediated suppression, providing an explanation for the apparent defect in immune regulation in HO-1(-/-) mice.