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

Fonte, Coralie; Kaminski, Sandra; Vanet, Anne; Lanfumey, Laurence; Cohen-Salmon, Charles; Ghislin, Stéphanie; Frippiat, Jean-Pol

doi:10.1096/fj.201800969r

Cited by 16 publications

(22 citation statements)

References 38 publications

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“…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.…”

Section: Resultssupporting

confidence: 57%

“…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.…”

Section: Calculation Of Dispersion Indexesmentioning

confidence: 99%

“…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.…”

Section: Potential Impact On Immunitymentioning

confidence: 99%

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

et al. 2020

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Immune dysregulation is among the main adverse outcomes of spaceflight. Despite the crucial role of the antibody repertoire in host protection, the effects of spaceflight on the human antibody repertoire are unknown. Consequently, using high-throughput sequencing, we examined the IgM repertoire of five cosmonauts 25 days before launch, after 64 ± 11 and 129 ± 20 days spent on the International Space Station (ISS), and at 1, 7, and 30 days after landing. This is the first study of this kind in humans. Our data revealed that the IgM repertoire of the cosmonauts was different from that of control subjects (n = 4) prior to launch and that two out the five analyzed cosmonauts presented significant changes in their IgM repertoire during the mission. These modifications persisted up to 30 days after landing, likely affected the specificities of IgM binding sites, correlated with changes in the V(D)J recombination process responsible for creating antibody genes, and coincided with a higher stress response. These data confirm that the immune system of approximately half of the astronauts who spent 6 months on the ISS is sensitive to spaceflight conditions, and 2 | BUCHHEIM Et al. F I G U R E 4 The cosmonaut IgM repertoire is different from that of the controls. A, Dot blots show individual dispersion indexes for unique VDJ associations in controls (n = 4) and cosmonauts (n = 5) at the beginning of the study (left panel) and 8 months later for controls or 7 days after landing for cosmonauts (right panel). B, Dot blots show the individual frequency of IGHV replacement footprints at the same time points. Statistically significant differences were found using unpaired t tests (A) and Mann-Whitney U tests (B). *P ≤ .

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Section: Resultssupporting

confidence: 57%

Section: Calculation Of Dispersion Indexesmentioning

confidence: 99%

Section: Potential Impact On Immunitymentioning

confidence: 99%

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

et al. 2020

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“…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.…”

Section: Discussionsupporting

confidence: 59%

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

Alauzet

Cunat

Wack

et al. 2020

Preprint

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Background: During deep-space travels, crewmembers face various physical and psychosocial stressors that could alter gut microbiota composition. Since it is well known that intestinal dysbiosis is involved in the onset or exacerbation of several disorders, the aim of this study was to evaluate changes in intestinal microbiota in a ground-based murine model mimicking psychosocial stressors encountered during a long-term space mission.Results: We demonstrate that 3 weeks of exposure to Chronic Unpredictable Mild Stress (CUMS) induce significant change in intracaecal β-diversity characterized by an important increase of the Firmicutes/Bacteroidetes ratio. These stress-induced alterations are associated with a decrease of Porphyromonadaceae, particularly of the genus Barnesiella that is a major member of gut microbiota in mice, but also in human, where it is described as having protective properties.Conclusions: These results raise the question of the impact of stress-induced decrease of beneficial taxa, support recent data obtained with in-flight experimentations or gravity change models, and emphasize the critical need for further studies exploring the impact of spaceflight on intestinal microbiota in order to propose strategies to countermeasure spaceflight-associated dysbiosis and its consequences on health.

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“…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.…”

Section: Effects On the Maturation Of Immune Cellsmentioning

confidence: 99%

Spaceflight-Associated Immune System Modifications

Jeandel¹,

Fonte²,

Calcagno³

et al. 2019

Beyond LEO - Human Health Issues for Deep Space Exploration [Working Title]

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Spaceflight is an adverse environment characterized by a unique combination of stressors affecting almost all physiological systems, including the immune system. Indeed, several studies have shown that about 50% of the astronauts have faced immunological troubles. Here, we will review how spaceflight affects immune cell development, innate as well as adaptive immunity, required to ensure an efficient protection of the host, with a particular focus on T and B cells. Indeed, to better appreciate the risks associated to future long-duration space missions and to develop pharmacologic or nutritional countermeasures allowing immune system protection, it is mandatory to fully understand how these cell types are affected by space conditions. Finally, we will compare immune changes observed in astronauts with those encountered in the elderly, thereby illustrating the societal interest of space research.

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

Cited by 16 publications

References 38 publications

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

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

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

Spaceflight-Associated Immune System Modifications

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