Radiation-induced decrease of CD8+ dendritic cells contributes to Th1/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 Th1 immunity, we tested the changes of Th1/Th2 response and found that IR caused a repression of Th1 immunity, indicating a possible role of CD8+DC in radiation-induced Th1/Th2 imbalance. We also found that a CD8+DC-inducing cytokine, Fms-like tyrosine kinase 3 ligand (FLT3 ligand), restored CD8+DC and reversed Th1/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 Th1/Th2 shift, which was reversed by Flt3 ligand treatment, suggesting a novel mechanism for radiation-induced immunosuppression.
Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, China.
Hu
H
Liu
Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, China.
Bailong
B
Li
Department of Radiation Oncology, The Second Hospital of Jilin University, Changchun, China, 130021.
Xiaojing
X
Jia
Department of Radiation Oncology, The Second Hospital of Jilin University, Changchun, China, 130021.
Yan
Y
Ma
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX75390, USA.
Yifeng
Y
Gu
Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, China.
Pei
P
Zhang
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX75390, USA; Department and Surgical Oncology and Institute of Clinical Medicine, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Qun
Q
Wei
Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, China.
Jianming
J
Cai
Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, China. Electronic address: cuijg@smmu.edu.cn.
Jianguo
J
Cui
Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, China. Electronic address: gaofusmmu@163.com.
Fu
F
Gao
Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, China. Electronic address: yyyang2010@163.com.
Yanyong
Y
Yang
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000528:radiation effects*; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000532:radiotherapy*; D011839:Radiation, Ionizing; D018417:Th1 Cells / Q000276:immunology / Q000528:radiation effects*; D058408:Th1-Th2 Balance / Q000528:radiation effects; D018418:Th2 Cells / Q000276:immunology / Q000528:radiation effects*; D018180:Thrombomodulin
D000954:Antigens, Surface; D016827:CD8 Antigens; D016207:Cytokines; D008565:Membrane Proteins; C546931:THBD protein, human; D018180:Thrombomodulin; C084881:flt3 ligand protein
DC subsets; Immune response; Ionizing radiation; Th1/Th2 shift