The Protective Effect of Chronic Intermittent Hypobaric Hypoxia on Preventing the Destruction of CD34⁺ Haematopoietic Stem Cells in Aplastic Anaemia by Modulating the Th1/Th2 Balance

Aplastic anaemia (AA) is a haematopoietic disorder caused by immune-mediated attack on haematopoietic stem cells (HSCs). Stem cell transplantation and immunosuppressive therapy remain the major treatment choice for AA patients but have limited benefits and undesired side effects. The aim of our study was to clarify the protective role of immunity of chronic intermittent hypobaric hypoxia (CIHH) and the underlying mechanism in AA. Our integrative analysis demonstrated that CIHH pre-treatment significantly improved haematopoiesis and survival in an AA rat model. We further confirmed that CIHH pre-treatment was closely associated with the Th1/Th2 balance and a large number of negative regulatory haematopoietic factors, such as TNF-alpha and IFN-gamma, produced by hyperactive Th1 lymphocytes released in AA rats, which induced the death program in a large number of CD34(+) HSCs by activating the Fas/FasL apoptosis pathway, while CIHH pre-treatment effectively downregulated the expression of TNF-alpha and IFN-gamma, resulting in a reduction in Fas antigen expression in CD34(+) HSCs. In summary, this study provides evidence that CIHH has good protective effect against AA by modulating immune balance in Th1/Th2 cells and may provide a new therapeutic strategy.