Immune modulation of CD4+CD25+ regulatory T cells by zoledronic acid

BMC Immunology

Research Article

Shih-Han Wang¹  Jo-Lin Lo²  Tsun-Mei Lin³  Ching-Ying Chen⁴  Shin-Cheh Chen⁵  Hsien Liu⁶ 

[1] Department of Chemical Engineering & Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, Taiwan;Department of Internal Medicine, E-DA Hospital/I-SHOU University, Kaohsiung, Taiwan;Department of Medical Laboratory Science, I-Shou University, Kaohsiung, Taiwan;Department of Medical Research, E-DA Hospital/I-SHOU University, Kaohsiung, Taiwan;Department of Laboratory Medicine, E-DA Hospital/I-SHOU University, Kaohsiung, Taiwan;Department of Medical Research, E-DA Hospital/I-SHOU University, Kaohsiung, Taiwan;Department of Surgery, Chang Gung Memorial Hospital, Taipei, Taiwan;Department of Surgery, Chi Mei Medical Center, Liouying, Tainan, Taiwan;Department of Chemical Engineering & Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, Taiwan;

关键词: Regulatory T cells;    Zoledronic acid;    Immunomodulation;    Breast cancer;   

DOI  :  10.1186/s12865-016-0183-7

 received in 2016-06-01, accepted in 2016-11-11,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundCD4+CD25+ regulatory T (Treg) cells suppress tumor immunity by inhibiting immune cells. Manipulation of Treg cells represents a new strategy for cancer treatment. Zoledronic acid (ZA), a nitrogen-containing bisphosphonate, inhibits the expression of receptor activator of nuclear factor kappa-B ligand (RANKL) on osteoblasts to inhibit osteoclastogenesis. In a mouse model of bisphosphonate-related osteonecrosis of the jaw, administration of ZA suppressed Treg-cell activity and activated inflammatory Th17 cells. However, the interaction between ZA and Treg cells remained unclear. This study investigated the immune modulation of Treg cells by ZA.MethodsFlow cytometry was used to analyze the phenotypic and immunosuppressive characteristics of Treg cells treated with ZA. Chemotactic migration was evaluated using transwell assays. Quantitative real-time PCR (qRT-PCR) was used to investigate the effect of ZA on the expression of suppressive molecules by Treg cells.ResultsProliferation of isolated Treg cells in culture was inhibited by ZA, although ZA did not induce apoptosis. qRT-PCR and flow cytometry showed that ZA significantly downregulated the expression of CCR4, CTLA4, PD-1 and RANKL on Treg cells. Chemotactic migration and immunosuppressive functions were also significantly attenuated in Treg cells pretreated with ZA, and these effects were dose-dependent. Co-culture with Treg cells significantly increased the migration rate of breast cancer cells, while pretreatment of Treg cells with ZA attenuated this effect.ConclusionsOur findings demonstrated that ZA acted as an immune modulator by significantly inhibiting the expansion, migration, immunosuppressive function and pro-metastatic ability of Treg cells. Immunomodulation of Treg cells by ZA represents a new strategy for cancer therapy.

【 授权许可】

CC BY   
© The Author(s). 2016