Radiation-induced decrease of CD8+dendritic cells contributes to Thl/Th2 shift

Exposure to ionizing radiation (IR) often reduce the helper T (Th) 1 like function, resulting in a Th1/Th2 imbalance, which could affect the efficacy of cancer radiotherapy. As the most potent antigen presenting cells, dendritic cells (DC) can be divided into several subsets with specialized function. However, there is no literature covering the changes of DC subsets and their roles in immune regulation in response to IR. In the present study, we were aimed to investigate the changes of DC subsets after IR and its relationship with Th1/Th2 immunity. We found a significant decrease of BDCA3 + DC in the blood of patients treated with radiotherapy. CD8 + DC, a mouse equivalent of human BDCA3 + DC, was also found decreased in mice spleen, peripheral blood and lymph node tissues after irradiation. As CD8 + DC mainly induce Thl immunity, we tested the changes of Thl /Th2 response and found that IR caused a repression of Th1 immunity, indicating a possible role of CD8 + DC in radiation-induced Thl/Fh2 imbalance. We also found that a CD8 + DC-inducing cytokine, Fms-like tyrosine kinase 3 ligand (FLT3 ligand), restored CD8 + DC and reversed Thl/Th2 shift. And then we found that bone marrow cells from irradiated mice differentiated into less CD8 + DC, which was also protected by FLT3 ligand. In conclusion, our data showed that IR induced a decrease of CD8 + DC and Thl/Th2 shift, which was reversed by Flt3 ligand treatment, suggesting a novel mechanism for radiation-induced immunosuppression. (C) 2017 Published by Elsevier B.V.