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Aberrant production of IL-13 by T cells promotes exocrinopathy in Id3 knockout mice

机译:T细胞异常产生IL-13会促进Id3基因敲除小鼠的外分泌病

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Elevated levels of the cytokine IL-13 has been found to be associated with autoimmune diseases, including Sj?gren's Syndrome. However, whether IL-13 plays a causative role in disease development is not known and cannot be easily studied in humans. Our previous work has shown that levels of IL-13 are elevated in Id3 knockout mice, which has been established as a model for primary Sj?gren's Syndrome. Here, we utilized an IL-13 reporter to determine the source of the elevated IL-13 levels observed in Id3 knockout mice and assess its contribution to SS pathology. Our results indicate that T cells, notably CD4 and γδ T cells, in Id3 knockout mice acquire IL-13 competency at an elevated rate well before disease symptoms become apparent. We also show that T cells developing early in life are more predisposed to produce IL-13. Finally, analysis of Id3 and IL-13 double deficient mice demonstrated that IL-13 plays an essential role in the deterioration of gland function. Our study provides crucial genetic evidence that enhanced IL-13 production by T cells can play a causative role in the exocrinopathy observed in Id3 knockout mice.
机译:已经发现细胞因子IL-13的水平升高与自身免疫性疾病有关,包括干燥综合征。然而,尚不清楚IL-13是否在疾病发展中起病因作用,并且在人中不容易研究。我们以前的工作表明,Id3基因敲除小鼠中IL-13的水平升高,该小鼠已被建立为原发性干燥综合征的模型。在这里,我们利用IL-13报告基因来确定在Id3基因敲除小鼠中观察到的IL-13水平升高的来源,并评估其对SS病理的影响。我们的结果表明,在疾病症状变得明显之前,Id3基因敲除小鼠中的T细胞(尤其是CD4和γδT细胞)以较高的速率获得了IL-13的能力。我们还显示,生命早期发育的T细胞更倾向于产生IL-13。最后,对Id3和IL-13双重缺陷小鼠的分析表明,IL-13在腺体功能退化中起着至关重要的作用。我们的研究提供了至关重要的遗传证据,表明T细胞增强的IL-13产生可在Id3基因敲除小鼠中观察到的外泌病中发挥致病作用。

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