机构：[1]Department of Infectious Diseases, Key Laboratory for Major Obsteric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China[2]State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China[3]Biological Resource Center, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China广东省中医院[4]College of Pharmacy, Guangzhou Medical University, Guangzhou, China[5]Key Laboratory of Immunology, Sino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou, China
Background Th cells (helper T cells) have multiple functions in Schistosoma japonicum (S. japonicum) infection. Inducible co-stimulator (ICOS) is induced and expressed in activated T lymphocytes, which enhances the development of B cells and antibody production through the ICOS/ICOSL pathway. It remains unclear about the role and possible regulating mechanism of ICOS+ Th cells in the spleen of S. japonicum-infected C57BL/6 mice. Methods C57BL/6 mice were infected with cercariae of S. japonicum through the abdomen. The expression of ICOS, activation markers, and the cytokine production on CD4(+) ICOS+ Th cells were detected by flow cytometry (FCM) and quantitative real-time PCR (qRT-PCR). Moreover, the differentially expressed gene data of ICOS+ and ICOS- Th cells from the spleen of infected mice were obtained by mRNA sequencing. Besides, Western blot and chromatin immunoprecipitation (ChIP) were used to explore the role of Ikzf2 on ICOS expression. Results After S. japonicum infection, the expression of ICOS molecules gradually increased in splenic lymphocytes, especially in Th cells (P < 0.01). Compared with ICOS- Th cells, more ICOS+ Th cells expressed CD69, CD25, CXCR5, and CD40L (P < 0.05), while less of them expressed CD62L (P < 0.05). Also, ICOS+ Th cells expressed more cytokines, such as IFN-gamma, IL-4, IL-10, IL-2, and IL-21 (P < 0.05). RNA sequencing results showed that many transcription factors were increased significantly in ICOS+ Th cells, especially Ikzf2 (P < 0.05). And then, the expression of Ikzf2 was verified to be significantly increased and mainly located in the nuclear of ICOS+ Th cells. Finally, ChIP experiments and dual-luciferase reporter assay confirmed that Ikzf2 could directly bind to the ICOS promoter in Th cells. Conclusion In this study, ICOS+ Th cells were found to play an important role in S. japonicum infection to induce immune response in the spleen of C57BL/6 mice. Additionally, Ikzf2 was found to be one important transcription factor that could regulate the expression of ICOS in the spleen of S. japonicum-infected C57BL/6 mice.
基金：
Natural Science
Foundation of China (81771696, 81802024), the Natural Science
Foundation of Guangdong Province (2020A1515010251,
2021A1515011032, 2018A030313217), and Guangzhou Science
and Technology Project (202002030082).
第一作者机构：[1]Department of Infectious Diseases, Key Laboratory for Major Obsteric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
共同第一作者：
通讯作者：
通讯机构：[2]State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China[4]College of Pharmacy, Guangzhou Medical University, Guangzhou, China[5]Key Laboratory of Immunology, Sino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou, China
推荐引用方式(GB/T 7714)：
Xie Shihao,Wei Haixia,Peng Anping,et al.Ikzf2 Regulates the Development of ICOS+ Th Cells to Mediate Immune Response in the Spleen of S. japonicum-Infected C57BL/6 Mice[J].FRONTIERS IN IMMUNOLOGY.2021,12:doi:10.3389/fimmu.2021.687919.
APA：
Xie, Shihao,Wei, Haixia,Peng, Anping,Xie, Anqi,Li, Jiajie...&Huang, Jun.(2021).Ikzf2 Regulates the Development of ICOS+ Th Cells to Mediate Immune Response in the Spleen of S. japonicum-Infected C57BL/6 Mice.FRONTIERS IN IMMUNOLOGY,12,
MLA：
Xie, Shihao,et al."Ikzf2 Regulates the Development of ICOS+ Th Cells to Mediate Immune Response in the Spleen of S. japonicum-Infected C57BL/6 Mice".FRONTIERS IN IMMUNOLOGY 12.(2021)
医学