These observations demonstrate that, normally, spaceflight affects the immune system of 50% of the astronauts and that immune dysregulations occurs during spaceflight, confirming in-flight dysregulation unique from your influences of landing and readaptation following deconditioning (Crucian et al., 2015, 2016a,b). There have been several studies to understand how spaceflight environment impairs innate immunity and T cell responses (reviewed in Guguinou et al., 2009; Frippiat et al., 2016). three groups: radiations, mechanical (microgravity and hypergravity), and socio-environmental (e.g., confinement, isolation, disrupted circadian rhythm) stressors. Medical and physiological findings from these missions have demonstrated that this extreme environment negatively impacts almost all physiological systems. It causes muscle mass atrophy, bone demineralization, cardiovascular and metabolic dysfunctions, impaired cognitive processes and reduces immunological competence. Concerning this last point, it was demonstrated that 15 of the 29 astronauts involved in Apollo missions developed bacterial or viral infections during, immediately after, or within 1 week of landing (Kimzey, 1977). In addition, the first study based on medical data collected on 46 astronauts who spent 6 months onboard the International Space Train station, showed that 46% of them had to face immunological problems (Crucian et al., 2016a). These observations demonstrate that, normally, spaceflight affects the immune system of 50% of the astronauts and that immune dysregulations happens during spaceflight, confirming in-flight Alosetron (Hydrochloride(1:X)) dysregulation unique from the influences of landing and readaptation following deconditioning (Crucian et al., 2015, 2016a,b). There have been several studies to understand how spaceflight environment impairs innate immunity and T cell reactions (examined in Guguinou et al., 2009; Frippiat et al., 2016). It has been shown the phagocytic and oxidative functions of neutrophils are affected by spaceflight conditions (Kaur et al., 2004; Rykova et al., 2008) and that astronauts monocytes show phenotypic and cytokine-production deregulations, a reduced ability to engulf as an animal model (Frippiat, 2013), we previously showed that Alosetron (Hydrochloride(1:X)) spaceflight affects antibody production in response to an antigenic activation (Boxio et al., 2005; Bascove et al., 2009). We also shown that somatic hypermutations, that diversify antibody-binding sites to improve their affinity, happen following immunization in space but at a rate of recurrence two-times lower than on Earth (Bascove et al., 2011). Another space experiment, coupled with several ground-based simulations of stressors experienced during a mission onboard the ISS, shown the transcription of IgM weighty chains and of an early B cell transcription element are revised only when embryos of are subjected to gravitational changes, suggesting a change in B lymphopoiesis (Huin-Schohn et al., 2013). Given the limitations in the availability and the experimental protocols that can be carried out with samples from astronauts as well Alosetron (Hydrochloride(1:X)) as the cost and the limited quantity of space experiments, various ground-based models have been developed to reproduce the effects of spaceflight conditions on an organism. The most Itgb1 widely used to reduce gravity constraint are head-down tilt bed rest for humans (Hargens and Vico, 2016) and anti-orthostatic tail suspension for rodents (Globus and Morey-Holton, 2016), while continuous centrifugation of animals are used to increase gravitational force. Recently, we showed that hypergravity and simulated microgravity (anti-orthostatic suspension) impair the proliferative reactions of murine lymphocytes (Guguinou et al., 2012; Gaignier et al., 2014). Moreover, we showed that anti-orthostatic suspension induces a decrease of murine B lymphopoiesis, demonstrating that our hypothesis deduced from studies performed with embryos that developed onboard the ISS was right (Lescale et al., 2015). In the same way, gravitational changes were shown to impact T cell development and the repertoire of T cell receptors, suggesting that sponsor immunity could be revised (Woods et al., 2003, 2005; Ghislin et al., 2015). However, gravitational changes are not the only stressors experienced during space missions. Socio-environmental factors (e.g., confinement, isolation, circadian rhythm misalignment) have to be regarded as because they can impact immune guidelines (Choukr, 2012; Frippiat et al., 2016). Here, to simulate socio-environmental tensions encountered during a space mission, we revealed adult male mice, as up to now most astronauts were males, to chronic unpredictable psychosocial and environmental stressors of various nature and slight intensity separated by resting periods (CUMS model). We chose this model, involving only slight stressors, because astronauts Alosetron (Hydrochloride(1:X)) are greatly qualified before soaring and are enthusiastic to go to space. This positive rewarding effect, understandable after such very long teaching, might compensate at least partially the negative effects of mission-associated stressors while for mice there is no rewarding effects. The second reason is that this model does not involve.