This year, we celebrate the 40th birthday of the first landing of humans on the moon. By 2020, astronauts should return to the lunar surface and establish an outpost there that will provide a technical basis for future manned missions to Mars. This paper summarizes major constraints associated with a trip to Mars, presents immunological hazards associated with this type of mission, and shows that our current understanding of the immunosuppressive effects of spaceflight is limited. Weakening of the immune system associated with spaceflight is therefore an area that should be considered more thoroughly before we undertake prolonged space voyages.

Understanding why the immune system is depressed during spaceflight is of obvious importance for future human deep-space missions, such as the foreseen missions to Mars. However, little is known about the effects of these flights on humoral immunity. We previously immunized adult Pleurodeles waltl (urodele amphibian) onboard the Mir space station and showed that heavy-chain variable (VH) domains of specific IgM antibodies are encoded by genes belonging to the VHII and VHVI families. We have now determined how these animals use their individual VHII and VHVI genes by screening IgM heavy-chain cDNA libraries and by quantifying IgM heavy-chain transcripts encoded by these genes. Results were compared with those obtained using control animals immunized on Earth under the same conditions as onboard Mir. Our experiments revealed an increase in the expression of IgM heavy-chain mRNAs encoded by the VHII and VHVI.C genes and a strong decrease in the expression of IgM heavy-chain mRNAs encoded by the VHVI.A and VHVI.B genes in spaceflight animals. Consequently, different heavy-chain mRNAs are expressed by spaceflight animals, demonstrating that this environment affects the humoral response. These observations may be due to a change in B-cell selection under spaceflight conditions.

Our previous research demonstrated that spaceflight conditions affect antibody production in response to an antigenic stimulation in adult amphibians. Here, we investigated whether antibody synthesis is affected when animal development occurs onboard a space station. To answer this question, embryos of the Iberian ribbed newt, Pleurodeles waltl, were sent to the International Space Station (ISS) before the initiation of immunoglobulin heavy-chain expression. Thus, antibody synthesis began in space. On landing, we determined the effects of spaceflight on P. waltl development and IgM heavy-chain transcription. Results were compared with those obtained using embryos that developed on Earth. We find that IgM heavy-chain transcription is doubled at landing and that spaceflight does not affect P. waltl development and does not induce inflammation. We also recreated the environmental modifications encountered by the embryos during their development onboard the ISS. This strategy allowed us to demonstrate that gravity change is the factor responsible for antibody heavy-chain transcription modifications that are associated with NF-κB mRNA level variations. Taken together, and given that the larvae were not immunized, these data suggest a modification of lymphopoiesis when gravity changes occur during ontogeny.

This study tests the hypothesis that the activators of peroxisome proliferator-activated receptors (PPARs) and 9-cis-retinoic acid receptor (RXR) regulate human semaphorin 6B (Sema6B) gene expression. The human MCF-7 breast adenocarcinoma cell line was chosen because it expresses Sema6B at a high level. The Sema6B mRNA level was analyzed by RT-PCR and the semaphorin 6B protein content was determined using a polyclonal antibody that we have produced and characterized. Treatments with fenofibrate (a PPAR· activator) and troglitazone (a PPARÁ ligand) strongly decreased the Sema6B mRNA. The drop in Sema6B mRNA level and in protein content was more important when the treatment combined the action of fenofibrate or troglitazone and 9-cis-retinoic acid.On the other hand, no significant change was observed in the Sema6B mRNA and protein levels when the cells were exposed to the combined action of GW610742 (a PPARß activator) and 9-cis-retinoic acid. These data suggest that PPAR·/RXR and PPARÁ/RXR heterodimers are involved in the regulation of Sema6B gene expression and open new perspectives concerning the participation of these nuclear receptors in cell recognition and migration.

a b s t r a c tC3 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 212.5 kDa. The deduced amino acid sequence showed that P. waltl C3 contains all the conserved domains known to be critical for C3 function. Quantitative real-time PCR (qRT-PCR) demonstrated that under normal physiological conditions, P. waltl C3 mRNA is expressed early during development because it is likely required for neurulation. Then, its expression increased as the immune system developed. In adults, the liver is the richest source of C3, though other tissues can also contribute. Further analysis of C3 expression demonstrated that C3 transcription increased when P. waltl larvae were exposed to pH or temperature stress, suggesting that environmental modifications might affect this animal's defenses against pathogens.