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

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. FASEB J. 33, 896–908 (2019). www.fasebj.org