Nrf2 alleviates spaceflight-induced immunosuppression and thrombotic microangiopathy in mice

Spaceflight-related stresses impact health via various body systems, including the haematopoietic and immune systems, with effects ranging from moderate alterations of homoeostasis to serious illness. Oxidative stress appears to be involved in these changes, and the transcription factor Nrf2, which regulates expression of a set of cytoprotective and antioxidative stress response genes, has been implicated in the response to spaceflight-induced stresses. Here, we show through analyses of mice from the MHU-3 project, in which Nrf2-knockout mice travelled in space for 31 days, that mice lacking Nrf2 suffer more seriously from spaceflight-induced immunosuppression than wild-type mice. We discovered that a one-month spaceflight-triggered the expression of tissue inflammatory marker genes in wild-type mice, an effect that was even more pronounced in the absence of Nrf2. Concomitant with induction of inflammatory conditions, the consumption of coagulation-fibrinolytic factors and platelets was elevated by spaceflight and further accelerated by Nrf2 deficiency. These results highlight that Nrf2 mitigates spaceflight-induced inflammation, subsequent immunosuppression, and thrombotic microangiopathy. These observations reveal a new strategy to relieve health problems encountered during spaceflight.

Automated summary

Through analyzing the MHU-3 project, where Nrf2-knockout mice were sent to space for 31 days, it was discovered that mice lacking Nrf2 experienced more severe immunosuppression compared to wild-type mice. Spaceflight also induced inflammation, which was further accelerated by Nrf2 deficiency through the consumption of coagulation-fibrinolytic factors and platelets. These findings highlight the role of Nrf2 in mitigating inflammation, immunosuppression, and thrombotic microangiopathy during spaceflight.