Transcriptomic dose-response by UVC and heavy ion radiation reveal pathways to immune impairment

Irradiation-induced immune impairment has been linked to human immune diseases, such as myelodysplastic syndromes (MDS) and leukemia. Global molecular responses to genome instability in immune cells can be identified by using transcriptomics. However, it is hard to link the molecular mechanism to the disease outcomes in the previous mechanistic studies. Here, transcriptomic dose-responses in human CD4+ T lymphocytes exposed to ultraviolet and heavy ion radiation were revealed by identification of the gene expression patterns of differential expression genes (DEGs) and calculating the point of departure (POD) of each DEG and molecular pathway, which provided an opportunity for quantitively illustrating the biological process of irradiation-induced immune impairments. Two potential adverse outcome pathways (AOPs) to irradiation-related leukemia were identified by mapping the molecular pathways into the biological event cascades, which provided phenotypic anchoring for the toxicological mechanisms. In addition, this study also revealed that NOP14/ NOP14-AS1 could be potential biomarkers of irradiation-induced immune impairment. Our works strengthen the use of AOP network in the next-generation risk assessment of irradiation-related diseases.