Halouani Aymen, Michaux Hélène, Jmii Habib, Trussart Charlotte, Chahbi Ahlem, Martens Henri, Renard Chantal, Aouni Mahjoub, Hober Didier, Geenen Vincent, Jaïdane Hela
Laboratoire des Maladies Transmissibles et Substances Biologiquement Actives LR99ES27, Faculté de Pharmacie de Monastir, Université de Monastir, Monastir 5000, Tunisia.
Faculté des Sciences de Tunis, Université de Tunis El Manar, Tunis 1068, Tunisia.
Microorganisms. 2021 Jul 19;9(7):1537. doi: 10.3390/microorganisms9071537.
Thymus plays a fundamental role in central tolerance establishment, especially during fetal life, through the generation of self-tolerant T cells. This process consists in T cells education by presenting them tissue-restricted autoantigens promiscuously expressed by thymic epithelial cells (TECs), thus preventing autoimmunity. Thymus infection by Coxsackievirus B (CV-B) during fetal life is supposed to disturb thymic functions and, hence, to be an inducing or accelerating factor in the genesis of autoimmunity. To further investigate this hypothesis, in our current study, we analyzed thymic expression of autoantigens, at the transcriptional and protein level, following in utero infection by CV-B4. mRNA expression levels of and , major autoantigens of pancreas and heart, respectively, were analyzed in whole thymus and in enriched TECs together along with both transcription factors, and , involved in autoantigens expression in the thymus. Results show that in utero infection by CV-B4 induces a significant decrease in and expression at both mRNA and protein level in whole thymus and in enriched TECs as well. Moreover, a correlation between viral load and autoantigens expression can be observed in the whole thymus, indicating a direct effect of in utero infection by CV-B4 on autoantigens expression. Together, these results indicate that an in utero infection of the thymus by CV-B4 may interfere with self-tolerance establishment in TECs by decreasing autoantigen expression at both mRNA and protein level and thereby increase the risk of autoimmunity onset.
胸腺在中枢耐受的建立过程中发挥着基础性作用，尤其是在胎儿期，通过产生自身耐受的T细胞来实现。这个过程包括通过向T细胞呈递由胸腺上皮细胞（TECs）广泛表达的组织限制性自身抗原，从而对T细胞进行教育，以此预防自身免疫。胎儿期柯萨奇病毒B（CV-B）感染胸腺被认为会干扰胸腺功能，因此是自身免疫发生的诱导或加速因素。为了进一步研究这一假设，在我们当前的研究中，我们分析了CV-B4宫内感染后，自身抗原在转录和蛋白质水平上的胸腺表达情况。分别在整个胸腺和富集的TECs中分析了胰腺和心脏的主要自身抗原 和 的mRNA表达水平，同时还分析了参与胸腺中自身抗原表达的两种转录因子 和 。结果表明，CV-B4宫内感染导致整个胸腺和富集的TECs中 和 在mRNA和蛋白质水平上的表达均显著下降。此外，在整个胸腺中可以观察到病毒载量与自身抗原表达之间的相关性，这表明CV-B4宫内感染对自身抗原表达有直接影响。总之，这些结果表明，CV-B4宫内感染胸腺可能通过在mRNA和蛋白质水平上降低自身抗原表达，从而干扰TECs中自身耐受的建立，进而增加自身免疫发病的风险。
