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.

Plasticity of the human IgM repertoire in response to long‐term spaceflight

“…We first analyzed the length of these regions and noted that this parameter is not impacted by spaceflight or during the recovery period (Figure 6A). The average length of IgM CDR3 was 15.7 amino acids (AA) in controls and cosmonauts, a value very close to the one (15.5 AA) determined in previous studies of IgM in healthy subjects 32,33 . Then, we wondered whether CDR3 amino acid composition could be affected.…”

“…Dispersion indexes were used to determine whether differences in the repertoire of VDJ associations, or other criteria, exist between groups or time points. 32 The following formula shows, for example, how these indexes (comprised between 0 and 1), were calculated for VDJ associations. These dispersion indexes take into account all associations whatever their frequencies of expression.…”

“…The average length of IgM CDR3 was 15.7 amino acids (AA) in controls and cosmonauts, a value very close to the one (15.5 AA) determined in previous studies of IgM in healthy subjects. 32,33 Then, we wondered whether CDR3 amino acid composition could be affected. We studied the position and the frequency of each amino acid along CDR3 sequences of 9 to 24 AA at the different time points.…”

Impact of a Model Used to Simulate Socio-Environmental Stressors Encountered During Spaceflight on Murine Intestinal Microbiota

“…This hypothesis is supported by higher serum corticosterone concentrations noticed in mice exposed to 3G during 21 days [41], as well as during the rst two weeks of exposition to the chronic mild stress model (CMS) which is more intense than CUMS because of water and food deprivation periods [42]. So, as previously reported for the TCRβ repertoire [43,44], socio-environmental stressors seem to have less impact on intestinal microbiota than gravity changes.…”

Spaceflight-Associated Immune System Modifications

“…This model involves the chronic exposure of mice to unpredictable socio-environmental stresses of various types (e.g., confinement, isolation, cage tilt, paired housing, perturbed circadian rhythm) and moderate intensity. It was demonstrated that this type of stressors only modifies 25% of the TCR repertoire [35]. Consequently, it appears that a change in the gravitational force has a much greater impact than socio-environmental stresses on the T-cell antigen receptor repertoire.…”