Hormetic Response to Low-Dose Radiation: Focus on the Immune System and Its Clinical Implications

Abstract

The interrelationship between ionizing radiation and the immune system is complex, multifactorial, and dependent on radiation dose/quality and immune cell type. High-dose radiation usually results in immune suppression. On the contrary, low-dose radiation (LDR) modulates a variety of immune responses that have exhibited the properties of immune hormesis. Although the underlying molecular mechanism is not fully understood yet, LDR has been used clinically for the treatment of autoimmune diseases and malignant tumors. These advancements in preclinical and clinical studies suggest that LDR-mediated immune modulation is a well-orchestrated phenomenon with clinical potential. We summarize recent developments in the understanding of LDR-mediated immune modulation, with an emphasis on its potential clinical applications.

Keywords: autoimmune disease; cancer therapy; hormesis; immune stimulating; immune therapy; low-dose radiation.

Figure 1

A model of LDR-induced hormetic effects on the immune system and their clinical indication. LDR has been shown to have dual effects on the regulation of immune hormesis. On the one hand, LDR could enhance the cytotoxicity of natural killer (NK) cells, promote the differentiation of mature dendritic cells (mDCs) and M1 macrophages (M1Φ), and activate T helper type 1 (Th1) cells and B cells (gray part of the figure), leading to the enhancement of the immune response, which can be applied in the treatment of malignant tumors. On the other hand, LDR regulates negative effects of the immune response by inhibiting the transformation of immature DCs (imDCs) to mDCs, inducing the differentiation of M2Φ, and stimulating a retention/expansion of Tregs (white part of the figure). This immunosuppressive activity can be used to control autoimmune diseases.