Socioenvironmental stressors encountered during spaceflight partially affect the murine TCR-β repertoire and increase its self-reactivity.

Abstract

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)-β repertoire. In this study, we investigated whether socioenvironmental stressors encountered during space missions affect T lymphopoiesis and the TCR-β 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-β repertoire were studied by flow cytometry and high-throughput sequencing, respectively. No change in thymocyte maturation or TCR expression were noted. TCR-β repertoire analysis revealed that 75% of neonate TCR-β sequences resulted from the expression of 3 variable (V)β 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-β 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-β repertoire and increase its self-reactivity.