Hind limb unloading, a model of spaceflight conditions, leads to decreased B lymphopoiesis similar to aging

Lescale, Chloé; Schenten, Véronique; Djeghloul, Dounia; Bennabi, Mériem; Gaignier, Fanny; Vandamme, Katleen; Strazielle, C.; Kuzniak, Isabelle; Petite, Hervé; Dosquet, Christine; Frippiat, Jean-Pol; Goodhardt, Michèle

doi:10.1096/fj.14-259770

Cited by 51 publications

(39 citation statements)

References 55 publications

(69 reference statements)

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“…Here, IL-7Rα transcript expression was not different in the thymuses of 2G pups. Similarly, in another study, we showed that hind limb unloading, which simulates microgravity, decreased early B cell differentiation and that this reduction is not due to a decrease in IL-7Rα expression on murine pro-B cells4.…”

Section: Discussionsupporting

confidence: 63%

“…These data suggest that gravitational changes can modify B lymphopoiesis3. This hypothesis was recently confirmed using hind limb unloaded mice, a ground-based model of microgravity, where a decrease in B lymphopoiesis was observed as of the common lymphoid progenitor stage with a major block at the pro-B to pre-B cell transition4. Furthermore, we showed that a long-term spaceflight affects the use of immunoglobulin heavy chain variable gene segments (VH) subgroups5 and the expression of individual VH gene segments6 in response to an antigenic stimulation in adult P. waltl , thereby suggesting that these conditions could affect the V(D)J recombination machinery.…”

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confidence: 64%

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Hypergravity exposure during gestation modifies the TCRβ repertoire of newborn mice

Ghislin

Ouzren-Zarhloul

Kaminski

et al. 2015

Sci Rep

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During spaceflight, organisms are subjected to mechanical force changes (gravity (G) changes) that affect the immune system. However, gravitational effects on lymphopoiesis have rarely been studied. Consequently, we investigated whether the TCRβ repertoire, created by V(D)J recombination during T lymphopoiesis, is affected by hypergravity exposure during murine development. To address this question, C57BL/6j mice were mated in a centrifuge so that embryonic development, birth and TCRβ rearrangements occurred at 2G. Pups were sacrificed at birth, and their thymus used to quantify transcripts coding for factors required for V(D)J recombination and T lymphopoiesis. We also created cDNA mini-libraries of TCRβ transcripts to study the impact of hypergravity on TCRβ diversity. Our data show that hypergravity exposure increases the transcription of TCRβ chains, and of genes whose products are involved in TCR signaling, and affects the V(D)J recombination process. We also observed that ~85% of the TCRβ repertoire is different between hypergravity and control pups. These data indicate that changing a mechanical force (the gravity) during ontogeny will likely affect host immunity because properties of loops constituting TCR antigen-binding sites are modified in hypergravity newborns. The spectrum of peptides recognized by TCR will therefore likely be different.

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Section: Discussionsupporting

confidence: 63%

mentioning

confidence: 64%

Hypergravity exposure during gestation modifies the TCRβ repertoire of newborn mice

Ghislin

Ouzren-Zarhloul

Kaminski

et al. 2015

Sci Rep

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“…; Lescale et al. ). Numerous studies indicate that body weight and body mass index are positively related to muscle, fat, and bone masses (Rosen and Bouxsein ; Muller et al.…”

Section: Discussionmentioning

confidence: 98%

The vestibular system is critical for the changes in muscle and bone induced by hypergravity in mice

et al. 2016

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Gravity changes concurrently affect muscle and bone as well as induce alterations in vestibular signals. However, the role of vestibular signals in the changes in muscle and bone induced by gravity changes remains unknown. We therefore investigated the effects of vestibular lesions (VL) on the changes in muscle and bone induced by 3 g hypergravity for 4 weeks in C57BL/6J mice. Quantitative computed tomography analysis revealed that hypergravity increased muscle mass surrounding the tibia and trabecular bone mineral content, adjusting for body weight in mice. Hypergravity did not affect cortical bone and fat masses surrounding the tibia. Vestibular lesions blunted the increases in muscle and bone masses induced by hypergravity. Histological analysis showed that hypergravity elevated the cross‐sectional area of myofiber in the soleus muscle. The mRNA levels of myogenic genes such as MyoD, Myf6, and myogenin in the soleus muscle were elevated in mice exposed to hypergravity. Vestibular lesions attenuated myofiber size and the mRNA levels of myogenic differentiation markers enhanced by hypergravity in the soleus muscle. Propranolol, a β‐blocker, antagonized the changes in muscle induced by hypergravity. In conclusion, this study is the first to demonstrate that gravity changes affect muscle and bone through vestibular signals and subsequent sympathetic outflow in mice.

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“…Changes in the maturation of granulocytic cells in the bone marrow of C57BL/6 mice were also reported after a 13 d spaceflight (8). Concerning lymphocyte development, it was shown that hindlimb unloading, a model frequently used to simulate spaceflight conditions, leads to decreased murine B lymphopoiesis, similar to aging (9). T lymphopoiesis was also shown to be sensitive to gravity changes, because reductions in CD4 + , CD8 + , and CD4 + CD8 + thymocyte populations were reported when murine fetal thymuses were cultured under clinorotation (10).…”

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confidence: 86%

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

et al. 2018

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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.

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Hind limb unloading, a model of spaceflight conditions, leads to decreased B lymphopoiesis similar to aging

Cited by 51 publications

References 55 publications

Hypergravity exposure during gestation modifies the TCRβ repertoire of newborn mice

Hypergravity exposure during gestation modifies the TCRβ repertoire of newborn mice

The vestibular system is critical for the changes in muscle and bone induced by hypergravity in mice

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

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