Socioenvironmental stressors encountered during spaceflight partially affect the murine TCR- repertoire and increase its self-reactivity
Socioenvironmental stressors encountered during spaceflight partially affect the murine TCR- repertoire and increase its self-reactivity
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DOI：
10.1096/fj.201800969r
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发表时间：
2019-01-01
期刊：
影响因子：
4.8
通讯作者：
Frippiat, Jean-Pol
中科院分区：
文献类型：
--
作者：
Fonte, Coralie;Kaminski, Sandra;Frippiat, Jean-Pol
众所周知，太空飞行会影响免疫系统。在先前的研究中，我们证明了小鼠发育期间的超重力暴露改变了85%的T细胞受体（TCR）库。在这项研究中，我们调查了在太空任务中遇到的社会环境压力是否会影响T淋巴细胞生成和TCR-库。为了解决这个问题，怀孕的小鼠在整个妊娠期都受到慢性不可预测的轻度应激源（CIMs）的影响，这是一种用于模拟太空任务期间遇到的社会环境压力的模型。然后，新生儿T淋巴细胞生成和TCR库分别通过流式细胞术和高通量测序进行了研究。未观察到胸腺细胞成熟或TCR表达的变化。TCR-库分析显示75%的新生儿TCR-序列由3个可变（V）区段的表达产生，并且该核心库不受CD 45的影响。然而，占全球总库25%的次要库对暴露于CO2敏感。我们还表明，变量（多样性）加入[V（D）J]重组过程不太可能受到影响。最后，我们注意到，与对照组幼仔相比，OHSS新生儿的次要功能更具自我反应性。这些发现表明，社会环境压力源，如在太空任务期间遇到的那些，影响TCR-库的一部分（25%），并且这些压力源可以增加自我反应性。Kaminski，S.，Vanet，A.，朗富梅湖Cohen-Salmon，C.，Ghislin，S.，Frippiat，J.太空飞行中遇到的社会环境压力因素部分影响小鼠TCR库并增加其自身反应性。
Spaceflights are known to affect the immune system. In a previous study, we demonstrated that hypergravity exposure during murine development modified 85% of the T-cell receptor (TCR)- repertoire. In this study, we investigated whether socioenvironmental stressors encountered during space missions affect T lymphopoiesis and the TCR- repertoire. To address this question, pregnant mice were subjected throughout gestation to chronic unpredictable mild stressors (CUMS), a model used to mimic socioenvironmental stresses encountered during space missions. Then, newborn T lymphopoiesis and the TCR- repertoire were studied by flow cytometry and high-throughput sequencing, respectively. No change in thymocyte maturation or TCR expression were noted. TCR- repertoire analysis revealed that 75% of neonate TCR- sequences resulted from the expression of 3 variable (V) segments and that this core repertoire was not affected by CUMS. However, the minor repertoire, representing 25% of the global repertoire, was sensitive to CUMS exposure. We also showed that the variable (diversity) joining [V(D)J] recombination process was unlikely to be affected. Finally, we noted that the CUMS neonatal minor repertoire was more self-reactive than the one of control pups. These findings show that socioenvironmental stressors such as those encountered during space missions affect a fraction (25%) of the TCR- repertoire and that these stressors could increase self-reactivity.Fonte, C., Kaminski, S., Vanet, A., Lanfumey, L., Cohen-Salmon, C., Ghislin, S., Frippiat, J.-P. Socioenvironmental stressors encountered during spaceflight partially affect the murine TCR- repertoire and increase its self-reactivity.