Transcriptome sequencing of splenic CD4+ T cells from systemically hypoxic mice
Despite significant advances in understanding cellular responses to hypoxia and the biology of hypoxia-inducible factors (HIFs), the impact of systemic hypoxia on immune responses, particularly in CD4+ T cells, remains understudied. This study aims to elucidate the molecular mechanisms underlying the effects of systemic hypoxia on the homeostasis of splenic CD4+ T cells. Specifically, we investigated how hypobaric hypoxia alters the transcriptomic landscape of CD4+ T cells and how these changes correlate with their metabolic stress response.We hypothesized that systemic hypoxia would induce distinct changes in the transcriptome of splenic CD4+ T cells, leading to an acute amino acid metabolic stress characterized by increased demand and decreased supply. To test this hypothesis, we performed transcriptome sequencing of splenic CD4+ T cells isolated from mice exposed to hypobaric hypoxia for varying durations. The primary objectives were to:Characterize the temporal changes in the transcriptome of splenic CD4+ T cells following systemic hypoxia exposure.Identify key signaling pathways and metabolic processes that are differentially regulated in response to hypoxia.Assess the impact of hypoxia-induced changes in the transcriptome on the survival and activation status of CD4+ T cells.Understanding the molecular mechanisms by which systemic hypoxia affects CD4+ T cell function is critical for developing strategies to mitigate the adverse effects of hypoxia on immune responses, which may have implications for various clinical conditions, including high-altitude acclimatization, respiratory viral infections, and severe respiratory distress syndromes. This study provides insights into the complex interplay between hypoxia and immune cell function, paving the way for potential therapeutic interventions aimed at enhancing immune resilience in hypoxic environments.