Transcriptome analysis of low-dose ionizing radiation-impacted genes in CD4+ T-cells undergoing activation and regulation of their expression of select cytokines

Immune cells are known as the most sensitive tissue for ionizing radiation. Numerous reports relating with the effect of low-dose ionizing radiation (LDIR) on immune activities showed that LDIR can induce immune-potentiation via modulating the activity of B-, T-, and NK cells, or macrophages, whereas high-dose radiation induces genome-wide apoptotic/necrotic tissue injury and immune suppression. Generally, CD4⁺ T-cells play pivotal roles in immune systems via cytokines and cell-surface molecules to activate other types of immune cells to eliminate the pathogen. In spite of the significance of CD4⁺ T-cells in the immune system, mechanism of how LDIR regulates CD4⁺ T-cell gene expression is poorly investigated. Thus, RNA-Seq and Gene-Set Enrichment Analysis (GSEA) analysis were done with low-dose irradiated (γ-radiation, 50 mGy, 204 mGy/h)/anti-CD3/CD28-stimulated CD4⁺ T-cells to explore the LDIR-specific regulation of CD4⁺ T-cell gene expression. The results indicated that the genes related to mRNA translation processes, mitochondrial function, cell cycle regulation, and cytokine induction were upregulated in irradiated cells. Moreover, this study showed that the expression of T-helper cell Type 1 (T_H1) or type 2 (T_H2) cytokine genes, such as those for interferon (IFN)-γ, interleukin (IL)-4, and IL-5 were increased by at least 1.4-fold in acute (204 mGy/h) or chronic (10 mGy/h) low-dose (10 or 50 mGy) irradiated/anti-CD3/CD28 stimulated CD4⁺ T-cells, whereas the T-regulatory (T_reg) cell cytokine gene, transforming growth factor (TGF)-β was decreased. Overall, these findings demonstrated that LDIR could cause an upregulation of selected immune product genes and, in turn, might modulate the activity of CD4⁺ T-cells undergoing activation via an impact on cytokine gene regulation.