Immune Cell Dysregulation in Hindlimb Unloading Mouse Model: Implications for Space Applications

Hindlimb unloading (HU) mice is a ground-based model that simulates the effects of microgravity. Since microgravity significantly affects the immune system, understanding immune cell function under these conditions is crucial for developing strategies to protect astronauts from infections and malignancies during long space missions.

To evaluate how microgravity affects neutrophils and T cells as the key components of innate and adaptive immunity, the activity of these cells in HU mice was compared with untreated control mice.

In this experimental study, 10 HU male BALB/c mice and 10 untreated control mice were included. Neutrophil-to-lymphocyte ratio (NLR) was evaluated and neutrophil function was assessed using the DHR assay. T cell proliferation was evaluated using the CFSE-dilution assay. IL-4 and IFN-ɣ production by T cell subsets was determined by intracellular cytokine staining with flow cytometry.

The capacity for reactive oxygen species (ROS) production in neutrophils did not differ between HU mice and control mice however, NLR was higher in HU mice. The proliferation of both CD4⁺ and CD8⁺ T cells was slightly reduced in HU mice. More notably, IL-4 production by CD4⁺ T cells and IFN-ɣ production by both CD4⁺ and CD8⁺ T cells were significantly decreased in HU mice.

Hindlimb unloading, simulating microgravity, impairs immune cell functions by reducing cytokine production and T cell proliferation. The increased NLR in HU mice could indicate a heightened inflammatory response. These insights are essential for advancing space biology and medicine, ensuring astronaut health during prolonged space travel.