Type I interferons attenuate T cell activating functions of human mast cells by decreasing TNF-α production and OX40 ligand expression while increasing IL-10 production
Type I interferons attenuate T cell activating functions of human mast cells by decreasing TNF-α production and OX40 ligand expression while increasing IL-10 production
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DOI：
10.1007/s10875-006-9043-1
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发表时间：
2006-11-01
影响因子：
9.1
通讯作者：
Hori, Toshiyuki
中科院分区：
文献类型：
--
作者：
Fujita, Tomoko;Kambe, Naotomo;Hori, Toshiyuki
最近的研究表明，肥大细胞不仅介导I型变态反应中的炎症反应，而且在获得性免疫中起重要作用。在本研究中，我们研究了与IFN-β具有相同受体的干扰素-α对人脐带血来源的肥大细胞的影响。肥大细胞产生TNF-α和IL-10，并在通过Fc β RI交联活化后表达OX 40配体。当用干扰素-α治疗时，TNF-α的产生减少，而IL-10和TGF-β的产生增加。此外，流式细胞术分析显示，干扰素-α下调肥大细胞上的OX 40配体的表达，这是肥大细胞-T细胞相互作用的关键。我们证实肥大细胞的活力不受干扰素-α治疗的影响。因此，与未经干扰素处理的肥大细胞相比，干扰素处理的肥大细胞诱导的CD 4（+）T细胞增殖水平较低。这些结果表明，I型干扰素通过其对肥大细胞的调节作用抑制T细胞免疫应答。
Recent studies have demonstrated that mast cells not only mediate inflammatory reactions in type I allergy but also play an important role in adaptive immunity. In the present study, we investigated the effects of interferon-alpha, which shares the same receptor as IFN-beta, on human cord blood-derived mast cells. Mast cells produced TNF-alpha, and IL-10, and expressed OX40 ligand upon activation by crosslinking of Fc epsilon RI. When treated with interferon-alpha, TNF-alpha production was decreased while IL-10 and TGF-beta productions were increased. Furthermore, flow cytometric analysis revealed that interferon-alpha downregulated expression OX40 ligand on mast cells which is crucial for mast cell-T cell interaction. We confirmed that the viability of mast cells was not affected by interferon-alpha treatment. Accordingly, interferon-alpha-treated mast cells induced lower levels of CD4(+) T cell proliferation compared with those without interferon-alpha treatment. These results suggest that type I interferons suppress T cell immune responses through their regulatory effects on mast cells.