Altered balance between self-reactive T helper (Th)17 cells and Th10 cells and between full-length forkhead box protein 3 (FoxP3) and FoxP3 splice variants in Hashimoto's thyroiditis
Altered balance between self-reactive T helper (Th)17 cells and Th10 cells and between full-length forkhead box protein 3 (FoxP3) and FoxP3 splice variants in Hashimoto's thyroiditis
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DOI：
10.1111/cei.12557
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发表时间：
2015-04-01
影响因子：
4.6
通讯作者：
Nielsen, C. H.
中科院分区：
文献类型：
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作者：
Kristensen, B.;Hegedues, L.;Nielsen, C. H.
辅助性T - 17 （Th17）细胞在自身免疫性疾病中起致病作用，而产生白细胞介素(IL)-10的Th10细胞起保护作用。两个亚群之间的平衡受局部细胞因子环境和完整叉头盒蛋白3 （FoxP3）相对于FoxP32（缺失外显子2）的相对表达调节。Th17和Th10细胞分化通常是通过多克隆刺激来研究的，对于自身免疫性甲状腺疾病中生理相关的自身抗原诱导Th17或Th10细胞分化的能力知之甚少。我们将健康供体和桥本甲状腺炎（HT）或格雷夫斯病（GD）患者的单核细胞进行多克隆刺激，或用人甲状腺球蛋白（TG）、人甲状腺过氧化物酶（TPO）或大肠杆菌脂多糖（LPS）刺激。TPO和LPS诱导HT患者初始CD4(+)CD45RA(+)CD45R0(-) T细胞向Th17细胞的分化增加。在多克隆刺激后，Th10细胞比例在HT中下降，但与抗原特异性刺激后的健康供者相当。综上所述，我们的数据显示，在甲状腺特异性自身抗原刺激后，HT患者发现Th17:Th10比例增加。我们还观察到IL-6和转化生长因子(TGF)-1以及编码FoxP32的mRNA的基线产量升高，而不是完整的FoxP3。这可能导致Th17细胞对HT的反应偏向。
T helper type 17 (Th17) cells play a pathogenic role in autoimmune disease, while interleukin (IL)-10-producing Th10 cells serve a protective role. The balance between the two subsets is regulated by the local cytokine milieu and by the relative expression of intact forkhead box protein 3 (FoxP3) compared to FoxP32, missing exon 2. Th17 and Th10 cell differentiation has usually been studied using polyclonal stimuli, and little is known about the ability of physiologically relevant self-antigens to induce Th17 or Th10 cell differentiation in autoimmune thyroid disease. We subjected mononuclear cells from healthy donors and patients with Hashimoto's thyroiditis (HT) or Graves' disease (GD) to polyclonal stimulation, or stimulation with human thyroglobulin (TG), human thyroid peroxidase (TPO), or Esherichiacoli lipopolysaccharide (LPS). TPO and LPS induced increased differentiation of naive CD4(+)CD45RA(+)CD45R0(-) T cells from HT patients into Th17 cells. Th10 cell proportions were decreased in HT after polyclonal stimulation, but were comparable to those of healthy donors after antigen-specific stimulation. Taken together, our data show that an increased Th17:Th10 ratio was found in HT patients after stimulation with thyroid-specific self-antigens. We also observed an elevated baseline production of IL-6 and transforming growth factor (TGF)-1 and of mRNA encoding FoxP32 rather than intact FoxP3. This may contribute to the skewing towards Th17 cell responses in HT.