Guoyang Zhang1,2, Ping Zhang3, Hongyun Liu1,2, Xiaoyan Liu1,2, Shuangfeng Xie1,2, Xiuju Wang1,2, Yudan Wu1,2, Jianxing Chang2,4, Liping Ma1,2. 1. a Department of Hematology , Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou , China. 2. b Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation , Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University , Guangzhou , China. 3. c Department of Hematology , Henan Provincial People's Hospital , Zhengzhou , China. 4. d Department of General Surgery , Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou , China.
Abstract
OBJECTIVES: The improved passive immune thrombocytopenia (ITP) mouse model has been extensively utilized for the study of ITP. However, how closely this model matches the human inflammation state and immune background is unclear. Our study aimed to explore the profile of Th cytokines and Th17/Treg cells in the model. METHODS: We induced the ITP mouse model by dose-escalation injection of MWReg30. The serum levels of cytokines (IFN-γ, IL-2, IL-4, IL-10, IL-17A, and TGF-β1) were measured by enzyme-linked immunosorbent assay and the frequency of Th17 and Treg cells was measured by flow cytometry. The mRNA expression of Foxp3 and RORrt was measured by real-time PCR. RESULTS: The serum levels of cytokines IFN-γ, TGF-β1, IL-4, and IL-10 were significantly lower in ITP mice. The secretion of serum proinflammatory cytokines IL-2 and IL-17A and the percentage of Th17 cells showed no statistically significant increase. In ITP mice the frequency of Treg cells and mRNA expression of Foxp3 was significantly lower in splenocytes. CONCLUSION: Our data suggest that the improved passive ITP mouse model does not mimic the autoimmune inflammatory process of human ITP. Compared with human ITP, this model has a similar change in frequency of Treg cells, which may directly or indirectly result from antibody-mediated platelet destruction due to attenuated release of TGF-β.
OBJECTIVES: The improved passive immune thrombocytopenia (ITP) mouse model has been extensively utilized for the study of ITP. However, how closely this model matches the humaninflammation state and immune background is unclear. Our study aimed to explore the profile of Th cytokines and Th17/Treg cells in the model. METHODS: We induced the ITP mouse model by dose-escalation injection of MWReg30. The serum levels of cytokines (IFN-γ, IL-2, IL-4, IL-10, IL-17A, and TGF-β1) were measured by enzyme-linked immunosorbent assay and the frequency of Th17 and Treg cells was measured by flow cytometry. The mRNA expression of Foxp3 and RORrt was measured by real-time PCR. RESULTS: The serum levels of cytokines IFN-γ, TGF-β1, IL-4, and IL-10 were significantly lower in ITP mice. The secretion of serum proinflammatory cytokines IL-2 and IL-17A and the percentage of Th17 cells showed no statistically significant increase. In ITP mice the frequency of Treg cells and mRNA expression of Foxp3 was significantly lower in splenocytes. CONCLUSION: Our data suggest that the improved passive ITP mouse model does not mimic the autoimmune inflammatory process of human ITP. Compared with human ITP, this model has a similar change in frequency of Treg cells, which may directly or indirectly result from antibody-mediated platelet destruction due to attenuated release of TGF-β.
Entities:
Keywords:
Immune thrombocytopenia; Th cytokines; Th17; Treg; mouse model