Hindlimb unloading, a physiological model of microgravity, modifies the murine bone marrow IgM repertoire in a similar manner as aging but less strongly.

Background: The spaceflight environment is an extreme environment that affects the immune system of approximately 50% of astronauts. With planned long-duration missions, such as the deployment of the Lunar Gateway and possible interplanetary missions, it is mandatory to determine how all components of the immune system are affected, which will allow the establishment of countermeasures to preserve astronaut health. However, despite being an important component of the immune system, antibody-mediated humoral immunity has rarely been investigated in the context of the effects of the space environment.

Corticosterone effects on postnatal cerebellar development in mice.

Glucocorticoids administered early in infancy can affect the architectonic organization of brain structures, particularly those with a postnatal development and resulting in long-term deficits of neuromotor function and cognition. The present study was undertaken to study the effects of daily corticosterone (CORT) injections at a pharmacological dose from postnatal days 8-15 on cerebellar and hippocampal development in mouse pups. Gene expression status for trophic factors involved in synaptic development and function as well as measures of layer thickness associated with cytochrome oxidase labelling were analyzed in the hippocampus, hypothalamus, and specific cerebellar lobules involved in motor control.

Long-duration head-down tilt bed rest confirms the relevance of the neutrophil to lymphocyte ratio and suggests coupling it with the platelet to lymphocyte ratio to monitor the immune health of astronauts.

The identification of safe and easily-determined-inflight biomarkers to monitor the immune system of astronauts is mandatory to ensure their well-being and the success of the missions. In this report, we evaluated the relevance of two biomarkers whose determination could be easily implemented in a spacecraft in the near future by using bedridden volunteers as a ground-based model of the microgravity of spaceflight. Our data confirm the relevance of the neutrophil to lymphocyte ratio (NLR) and suggest platelet to lymphocyte ratio (PLR) monitoring to assess long-lasting immune diseases.

Link between the EZH2 noncanonical pathway and microtubule organization center polarization during early T lymphopoiesis.

EZH2 plays an essential role at the β-selection checkpoint of T lymphopoiesis by regulating histone H3 lysine 27 trimethylation (H3K27me3) via its canonical mode of action. Increasing data suggest that EZH2 could also regulate other cellular functions, such as cytoskeletal reorganization, via its noncanonical pathway. Consequently, we investigated whether the EZH2 noncanonical pathway could be involved in early T-cell maturation, which requires cell polarization.

B-Cell Homeostasis Is Maintained During Two Months of Head-Down Tilt Bed Rest With or Without Antioxidant Supplementation.

Alterations of the immune system could seriously impair the ability to combat infections during future long-duration space missions. However, little is known about the effects of spaceflight on the B-cell compartment. Given the limited access to astronaut samples, we addressed this question using blood samples collected from 20 healthy male volunteers subjected to long-duration bed rest, an Earth-based analog of spaceflight.

Gravitational Experimental Platform for Animal Models, a New Platform at ESA's Terrestrial Facilities to Study the Effects of Micro- and Hypergravity on Aquatic and Rodent Animal Models.

Using rotors to expose animals to different levels of hypergravity is an efficient means of understanding how altered gravity affects physiological functions, interactions between physiological systems and animal development. Furthermore, rotors can be used to prepare space experiments, e.g.

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

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.

Modulation of Iberian Ribbed Newt Complement Component C3 by Stressors Similar to those Encountered during a Stay Onboard the International Space Station.

The complement system plays an important role in inflammation, innate and acquired immunity, as well as homeostasis. Despite these functions, the effects of spaceflight conditions on the complement system have not yet been intensively studied. Consequently, we investigated the effects of five types of chronic stressors, similar to those encountered during a stay onboard the International Space Station, on C3 expression in larvae of the urodele amphibian .

Analysis of femurs from mice embarked on board BION-M1 biosatellite reveals a decrease in immune cell development, including B cells, after 1 wk of recovery on Earth.

Bone loss and immune dysregulation are among the main adverse outcomes of spaceflight challenging astronauts' health and safety. However, consequences on B-cell development and responses are still under-investigated. To fill this gap, we used advanced proteomics analysis of femur bone and marrow to compare mice flown for 1 mo on board the BION-M1 biosatellite, followed or not by 1 wk of recovery on Earth, to control mice kept on Earth.

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.

The urodele amphibian Pleurodeles waltl has a diverse repertoire of immunoglobulin heavy chains with polyreactive and species-specific features.

Urodele amphibians are an interesting model because although they possess the cardinal elements of the vertebrate immune system, their immune response is apparently subdued. This phenomenon, sometimes regarded as a state of immunodeficiency, has been attributed by some authors to limited antibody diversity. We reinvestigated this issue in Pleurodeles waltl, a metamorphosing urodele, and noted that upsilon transcripts of its IgY repertoire were as diverse as alpha transcripts of the mammalian IgA repertoire.

Hypergravity exposure during gestation modifies the TCRβ repertoire of newborn mice.

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.

Molecular cloning and expression analysis of Pleurodeles waltl complement component C3 under normal physiological conditions and environmental stresses.

C3 is a component of the complement system that plays a central role in immunity, development and tissue regeneration. In this study, we isolated the C3 cDNA of the Iberian ribbed newt Pleurodeles waltl. This cDNA encodes a 1637 amino acid protein with an estimated molecular mass of 212.

LFA-1 and ICAM-1 expression induced during melanoma-endothelial cell co-culture favors the transendothelial migration of melanoma cell lines in vitro.

Background: Patients with metastatic melanoma have a poor median rate of survival. It is therefore necessary to increase our knowledge about melanoma cell dissemination which includes extravasation, where cancer cells cross the endothelial barrier. Extravasation is well understood during travelling of white blood cells, and involves integrins such as LFA-1 (composed of two chains, CD11a and CD18) expressed by T cells, while ICAM-1 is induced during inflammation by endothelial cells.

PHF19 and Akt control the switch between proliferative and invasive states in melanoma.

Melanoma tumor cells shift between proliferative and invasive states based on their plasticity and microenvironmental conditions. Our team has shown that melanoma cells, grown as spheroids in a neural cell crest medium, polarize toward an invasive phenotype, characterized by a higher motility, a poor proliferation rate and a gain of pluripotency gene expression (Nanog and Oct4) when compared with cells grown in two dimensions in a serum-contaning medium. In agreement with the phenotypic switching hypothesis, most of these features are reversible.

Plasticity of melanoma cells induced by neural cell crest conditions and three-dimensional growth.

Melanoma tumors have been shown to comprise both invasive and proliferative cell subpopulations. These populations are highly plastic, thus hampering full characterization and therapeutic targeting of dormant and partially dedifferentiated invasive cells. We have reported, previously, that melanoma cells grown in a serum-free neural crest medium, in which they propagate as spheroids, show higher invasiveness and increased immune escape.

Nanog and Oct4 overexpression increases motility and transmigration of melanoma cells.

Purpose: Melanoma tumors are highly heterogeneous and can undergo phenotypic modifications depending on their plasticity and the microenvironment, with shifts between proliferative and invasive states. We have shown that melanoma cells, grown as spheroids in a neural crest cell medium, polarize toward an invasive and motile phenotype, in agreement with transcriptomic modulations, including the up-regulation of Nanog and Oct4. Overexpression of these genes was shown to be associated with poor prognosis and metastatic forms of some cancers.

Junctional adhesion molecules are required for melanoma cell lines transendothelial migration in vitro.

One of the main steps of metastasis is extravasation, a phenomenon well described in lymphocytes but remaining to be fully uncovered for melanoma. Junctional adhesion molecules (JAMs) control the transendothelial migration of leukocytes. To date, the role of the JAM proteins, notably JAM-A and JAM-C, has not been examined in melanoma.

Coexpression of major histocompatibility complex class II with chemokines and nuclear NFkappaB p50 in melanoma: a rational for their association with poor prognosis.

The constitutive expression of major histocompatibility complex class II (MHC II) molecules in melanoma is highly unusual and has been associated with unfavorable clinical outcome and higher metastatic dissemination. This association remains poorly understood and therefore, in this study we looked to whether it is caused by intracellular events that promote tumor progression. We previously reported that MHC II expression in melanoma cells requires active mitogen-activated protein kinase/extracellular signal-related kinase.