Abnormal natural killer cell function in systemic sclerosis: Altered cytokine production and defective killing activity
Abnormal natural killer cell function in systemic sclerosis: Altered cytokine production and defective killing activity
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DOI：
10.1111/j.0022-202x.2005.23767.x
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发表时间：
2005-10-01
影响因子：
6.5
通讯作者：
Sato, S
中科院分区：
文献类型：
--
作者：
Horikawa, M;Hasegawa, M;Sato, S
自然杀伤 (NK) 细胞是先天免疫效应细胞，可产生各种免疫调节细胞因子。最近的研究表明，NK 细胞参与自身免疫的启动。在这项研究中，我们通过评估频率和绝对数量、激活标记物表达、细胞因子产生和杀伤活性，确定了系统性硬化症 (SSc)（一种自身免疫性结缔组织疾病）中 NK 细胞的异常。弥漫性皮肤 SSc (dcSSc) 中 NK 细胞的频率和绝对数量增加，而局限性皮肤 SSc (IcSSc) 中 NK 细胞的频率和绝对数量正常。来自 dcSSc 和 IcSSc 患者的 NK 细胞均表现出激活的表型，其特征是 CD16 和 CD69 表达上调，CD62L 表达下调。与正常对照相比，来自 dcSSc 和 IcSSc 患者的未刺激 NK 细胞产生的干扰素 (IFN)-γ 量有所增加，而在刺激时，产生的 IFN-γ 量减少。 dcSSc 患者中，未经刺激的 NK 细胞产生的白细胞介素 (IL)-5 和 IL-10 以及受刺激的 NK 细胞产生的 IL-6 增加，但在 IcSSc 患者中则没有增加。尽管未经刺激的 NK 细胞产生的细胞因子增加，但来自 dcSSc 和 IcSSc 患者的 NK 细胞的天然细胞毒性活性和颗粒酶 B 分泌却减少。这些结果表明 NK 细胞功能的改变导致了 SSc 的免疫异常。
Natural killer (NK) cells are innate immune effectors that produce various immunoregulatory cytokines. Recent studies have shown that NK cells are involved in the initiation of autoimmunity. In this study, we determined abnormalities of NK cells in systemic sclerosis (SSc), an autoimmune connective tissue disease, by assessing the frequency and absolute number, activation marker expression, cytokine production, and killing activity. The frequency and absolute number of NK cells increased in diffuse cutaneous SSc (dcSSc), whereas they were normal in limited cutaneous SSc (IcSSc). NK cells from both dcSSc and IcSSc patients exhibited activated phenotypes characterized by up-regulated CD16 and CD69 expression and downregulated CD62L expression. Interferon (IFN)-gamma production by non-stimulated NK cells from both dcSSc and IcSSc patients was increased compared to the normal control, whereas on stimulation, a reduced amount of IFN-gamma was produced. Interleukin (IL)-5 and IL-10 production by non-stimulated NK cells and IL-6 production by stimulated NK cells were augmented in dcSSc patients, but not in IcSSc patients. Despite the augmented cytokine production by non-stimulated NK cells, natural cytotoxicity activity and granzyme B secretion was reduced in NK cells from dcSSc and IcSSc patients. These results suggested that altered NK cell function contributes to immunological abnormalities in SSc.