PDF(Pubmed)
Abstract：
Autoimmune thyroid diseases (AITDs) are prevalent disorders, primarily encompassing Graves\' disease (GD) and Hashimoto\'s thyroiditis (HT). Despite their common occurrence, the etiology of AITDs remains elusive. Th9 cells, a new subset of CD4+T cells with immunomodulatory properties, have been linked to the development of various autoimmune diseases. However, research on the role of Th9 cells in AITDs is limited.
We investigated the expression of Th9 cells,their functional cytokine IL-9, and transcription factor IRF4 in peripheral blood mononuclear cells (PBMCs) and plasma of AITD patients and healthy controls. Additionally, we explored the genetic association between four loci polymorphisms (rs31564, rs2069879, rs1859430, and rs2069868) of the IL-9 gene and AITDs.
We reported, for the first time, that refractory GD patients exhibited elevated mRNA levels of IL-9 and IRF4 in PBMCs, increased IL-9 protein levels in plasma, and a higher proportion of Th9 cells in peripheral blood when compared to normal controls. Furthermore, human recombinant IL-9 protein was found to enhance IFN-g secretion in PBMCs from both GD patients and normal controls. At the genetic association level, after adjusting for age and sex, the rs2069879 polymorphism exhibited a significant association with AITDs under an additive model (P<0.001, OR= 0.05, 95% CI=0.03-0.08).
Our results reveal that Th9 cells may exert a pivotal role in the pathogenesis and progression of refractory GD and HT, and IL-9 holds promise as a novel therapeutic target for the management of AITDs.
We investigated the expression of Th9 cells,their functional cytokine IL-9, and transcription factor IRF4 in peripheral blood mononuclear cells (PBMCs) and plasma of AITD patients and healthy controls. Additionally, we explored the genetic association between four loci polymorphisms (rs31564, rs2069879, rs1859430, and rs2069868) of the IL-9 gene and AITDs.
We reported, for the first time, that refractory GD patients exhibited elevated mRNA levels of IL-9 and IRF4 in PBMCs, increased IL-9 protein levels in plasma, and a higher proportion of Th9 cells in peripheral blood when compared to normal controls. Furthermore, human recombinant IL-9 protein was found to enhance IFN-g secretion in PBMCs from both GD patients and normal controls. At the genetic association level, after adjusting for age and sex, the rs2069879 polymorphism exhibited a significant association with AITDs under an additive model (P<0.001, OR= 0.05, 95% CI=0.03-0.08).
Our results reveal that Th9 cells may exert a pivotal role in the pathogenesis and progression of refractory GD and HT, and IL-9 holds promise as a novel therapeutic target for the management of AITDs.
摘要：
■自身免疫性甲状腺疾病（AITDs）是普遍存在的疾病，主要包括格雷夫斯病（GD）和桥本甲状腺炎（HT）。尽管它们很常见，AITDs的病因仍然难以捉摸。Th9细胞，一个新的具有免疫调节特性的CD4+T细胞亚群，与各种自身免疫性疾病的发展有关。然而,Th9细胞在AITDs中的作用研究有限。
■我们研究了Th9细胞的表达，AITD患者和健康对照组外周血单个核细胞（PBMC）和血浆中的功能性细胞因子IL-9和转录因子IRF4。此外,我们探索了IL-9基因的四个位点多态性（rs31564，rs2069879，rs1859430和rs2069868）与AITDs之间的遗传关联。
■我们报道，第一次,难治性GD患者PBMC中IL-9和IRF4的mRNA水平升高，血浆中IL-9蛋白水平升高，与正常对照组相比，外周血中Th9细胞的比例更高。此外，发现人重组IL-9蛋白可增强GD患者和正常对照PBMC中IFN-g的分泌。在遗传关联层面，在调整了年龄和性别后，在加性模型下,rs2069879多态性与AITDs显著相关(P<0.001,OR=0.05,95%CI=0.03-0.08).
■我们的结果表明，Th9细胞可能在难治性GD和HT的发病和进展中起关键作用，IL-9有望成为治疗AITDs的新靶点。
■我们研究了Th9细胞的表达，AITD患者和健康对照组外周血单个核细胞（PBMC）和血浆中的功能性细胞因子IL-9和转录因子IRF4。此外,我们探索了IL-9基因的四个位点多态性（rs31564，rs2069879，rs1859430和rs2069868）与AITDs之间的遗传关联。
■我们报道，第一次,难治性GD患者PBMC中IL-9和IRF4的mRNA水平升高，血浆中IL-9蛋白水平升高，与正常对照组相比，外周血中Th9细胞的比例更高。此外，发现人重组IL-9蛋白可增强GD患者和正常对照PBMC中IFN-g的分泌。在遗传关联层面，在调整了年龄和性别后，在加性模型下,rs2069879多态性与AITDs显著相关(P<0.001,OR=0.05,95%CI=0.03-0.08).
■我们的结果表明，Th9细胞可能在难治性GD和HT的发病和进展中起关键作用，IL-9有望成为治疗AITDs的新靶点。
