Ji Yang1,2, Xue Yang3,4, Jie Yang3,4, Ming Li1,2. 1. From the Department of Dermatology, Zhongshan Hospital, Fudan University; Division of Rheumatology, Huashan Hospital, Fudan University; Institute of Rheumatology, Immunology and Allergy, Fudan University; Blood Engineering Lab, Shanghai Blood Center, Shanghai, China. yang.hua@yeah.net li.ming@zs-hospital.sh.cn. 2. Ji Yang, MD, PhD, Department of Dermatology, Zhongshan Hospital, Fudan University; X. Yang, MD, PhD, Division of Rheumatology, Huashan Hospital, and Institute of Rheumatology, Immunology and Allergy, Fudan University; Jie Yang, PhD, Blood Engineering Lab, Shanghai Blood Center; M. Li, MD, PhD, Department of Dermatology, Zhongshan Hospital, Fudan University. Ji Yang, Xue Yang, and Jie Yang contributed equally to this work. yang.hua@yeah.net li.ming@zs-hospital.sh.cn. 3. From the Department of Dermatology, Zhongshan Hospital, Fudan University; Division of Rheumatology, Huashan Hospital, Fudan University; Institute of Rheumatology, Immunology and Allergy, Fudan University; Blood Engineering Lab, Shanghai Blood Center, Shanghai, China. 4. Ji Yang, MD, PhD, Department of Dermatology, Zhongshan Hospital, Fudan University; X. Yang, MD, PhD, Division of Rheumatology, Huashan Hospital, and Institute of Rheumatology, Immunology and Allergy, Fudan University; Jie Yang, PhD, Blood Engineering Lab, Shanghai Blood Center; M. Li, MD, PhD, Department of Dermatology, Zhongshan Hospital, Fudan University. Ji Yang, Xue Yang, and Jie Yang contributed equally to this work.
Abstract
OBJECTIVE: Hydroxychloroquine (HCQ) is a commonly used medicine for the treatment of systemic lupus erythematosus (SLE), and Th17 cells are closely related to the pathogenesis of SLE. However, the role and mechanism of HCQ on Th17 cell differentiation in SLE is not clearly understood. Here, we investigate the effect of HCQ on Th17 cell differentiation both in vitro and in patients with SLE. METHODS: Twenty-five patients with SLE were divided into 2 treatment groups: prednisone alone and HCQ plus prednisone. Interleukin 17 (IL-17) expression was analyzed by ELISA and real-time (RT)-PCR. Th17 were measured in patients with SLE by flow cytometry before and after HCQ treatment. In vitro, naive T cells were cultured in Th17-inducing conditions with or without HCQ. Cell differentiation and IL-17 expression were analyzed. Finally, transcriptome sequencing identified differential gene expression between naive T cells and induced Th17 cells. RESULTS: In patients, HCQ plus prednisone treatment inhibited IL-17 production, gene expression, and Th17 cell differentiation. In vitro, HCQ inhibited Th17 cell proliferation and differentiation, as well as IL-17 production. Five microRNA were significantly different in Th17 cells compared with naive T cells, and HCQ treatment reversed this effect. In vivo, microRNA-590 (miR-590) was verified and was significantly decreased in Th17 cells, compared with naive T cells from lupus-prone mice. Moreover, miR-590 was increased in patients treated with HCQ plus prednisone. CONCLUSION: HCQ inhibited Th17 cell differentiation and IL-17 production both in vitro and in patients with SLE. Our study provides additional evidence for HCQ as a treatment for SLE.
OBJECTIVE:Hydroxychloroquine (HCQ) is a commonly used medicine for the treatment of systemic lupus erythematosus (SLE), and Th17 cells are closely related to the pathogenesis of SLE. However, the role and mechanism of HCQ on Th17 cell differentiation in SLE is not clearly understood. Here, we investigate the effect of HCQ on Th17 cell differentiation both in vitro and in patients with SLE. METHODS: Twenty-five patients with SLE were divided into 2 treatment groups: prednisone alone and HCQ plus prednisone. Interleukin 17 (IL-17) expression was analyzed by ELISA and real-time (RT)-PCR. Th17 were measured in patients with SLE by flow cytometry before and after HCQ treatment. In vitro, naive T cells were cultured in Th17-inducing conditions with or without HCQ. Cell differentiation and IL-17 expression were analyzed. Finally, transcriptome sequencing identified differential gene expression between naive T cells and induced Th17 cells. RESULTS: In patients, HCQ plus prednisone treatment inhibited IL-17 production, gene expression, and Th17 cell differentiation. In vitro, HCQ inhibited Th17 cell proliferation and differentiation, as well as IL-17 production. Five microRNA were significantly different in Th17 cells compared with naive T cells, and HCQ treatment reversed this effect. In vivo, microRNA-590 (miR-590) was verified and was significantly decreased in Th17 cells, compared with naive T cells from lupus-prone mice. Moreover, miR-590 was increased in patients treated with HCQ plus prednisone. CONCLUSION:HCQ inhibited Th17 cell differentiation and IL-17 production both in vitro and in patients with SLE. Our study provides additional evidence for HCQ as a treatment for SLE.
Authors: Eric A Meyerowitz; Augustin G L Vannier; Morgan G N Friesen; Sara Schoenfeld; Jeffrey A Gelfand; Michael V Callahan; Arthur Y Kim; Patrick M Reeves; Mark C Poznansky Journal: FASEB J Date: 2020-04-29 Impact factor: 5.191
Authors: Gerwyn Morris; Eugene Athan; Ken Walder; Chiara C Bortolasci; Adrienne O'Neil; Wolf Marx; Michael Berk; André F Carvalho; Michael Maes; Basant K Puri Journal: Life Sci Date: 2020-10-06 Impact factor: 6.780