Functional defects in CD4(+) CD25(high) FoxP3(+) regulatory cells in ankylosing spondylitis.
Functional defects in CD4(+) CD25(high) FoxP3(+) regulatory cells in ankylosing spondylitis.
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DOI：
10.1038/srep37559
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发表时间：
2016-11-30
影响因子：
4.6
通讯作者：
Zhu P
中科院分区：
文献类型：
--
作者：
Guo H;Zheng M;Zhang K;Yang F;Zhang X;Han Q;Chen ZN;Zhu P
叉头盒P3（FoxP 3）阳性调节性T细胞（Treg）在自身免疫耐受的维持中起关键作用，并且Treg功能障碍已涉及许多自身免疫性疾病。强直性脊柱炎（AS）的发病机制中是否有TGFAP的参与，以及TGFAP的作用机制尚未完全阐明。在这里，我们研究了Treg功能，发现活动性AS患者外周血（PB）中的TcR具有低于健康对照的FoxP 3平均荧光强度（MFI），并且不能完全抑制幼稚T细胞（Tn）增殖。我们还研究了在这种情况下PB Treg功能障碍的机制，发现PB Treg不能有效地利用IL-2，并且在活动性AS中具有相对较少的STAT 5磷酸化。此外，来自活动性AS患者的PB T细胞在FOXP 3基因的CNS 2区域表现出更高的CpG岛甲基化。因此，我们的研究结果表明，功能缺陷的THEORY存在于AS。异常的IL-2信号传导和异常的CNS 2表观遗传控制诱导PB Tfos的功能缺陷，并代表了AS发病的潜在新机制。这些发现可能有助于设计新的AS治疗方法。
Forkhead box P3 (FoxP3)-positive regulatory T cells (Tregs) play a pivotal role in the preservation of self-tolerance, and Treg dysfunction has been implicated in many autoimmune diseases. Whether and how Tregs participate in the pathogenesis of ankylosing spondylitis (AS) has not been fully elucidated. Here, we investigated Treg function and found that Tregs in peripheral blood (PB) from patients with active AS had lower FoxP3 mean fluorescence intensity (MFI) than those from healthy controls and could not fully suppress naïve T cell (Tn) proliferation. We also studied the mechanisms underlying PB Treg dysfunction in this context and found that PB Tregs failed to effectively utilize IL-2 and had relatively little STAT5 phosphorylation in active AS. Moreover, PB Tregs from patients with active AS exhibited greater CpG island methylation in the CNS2 region of the FOXP3 gene. Therefore, our findings indicate that functional defects in Tregs are present in AS. Abnormal IL-2 signalling and aberrant CNS2 epigenetic control induced functional defects in PB Tregs and represents a potential new mechanism for AS pathogenesis. These findings may aid the design of new treatment approaches for AS.
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控制FOXP3基因座中的顺式元素对调节T细胞身份的遗传控制。
影响因子：
64.5
作者：
Feng Y;Arvey A;Chinen T;van der Veeken J;Gasteiger G;Rudensky AY
通讯作者：
Rudensky AY
影响因子：
20.3
作者：
Borsellino, Giovanna;Kleinewietfeld, Markus;Falk, Kirsten
通讯作者：
Falk, Kirsten
DOI：
10.4049/jimmunol.1003224
发表时间：
2011-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Long SA;Buckner JH
通讯作者：
Buckner JH
影响因子：
82.9
作者：
Carbone, Fortunata;De Rosa, Veronica;Matarese, Giuseppe
通讯作者：
Matarese, Giuseppe
影响因子：
8.7
作者：
Shevach EM;Thornton AM
通讯作者：
Thornton AM