Ikzf2 Regulates the Development of ICOS+ Th Cells to Mediate Immune Response in the Spleen of S. japonicum-Infected C57BL/6 Mice
BackgroundTh 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 rema...
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Frontiers Media S.A.
2021-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.687919/full |
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| author | Shihao Xie Haixia Wei Anping Peng Anqi Xie Jiajie Li Chao Fang Feihu Shi Quan Yang He Huang Hongyan Xie Xingfei Pan Xu Tian Xu Tian Jun Huang Jun Huang |
| author_facet | Shihao Xie Haixia Wei Anping Peng Anqi Xie Jiajie Li Chao Fang Feihu Shi Quan Yang He Huang Hongyan Xie Xingfei Pan Xu Tian Xu Tian Jun Huang Jun Huang |
| author_sort | Shihao Xie |
| collection | DOAJ |
| description | BackgroundTh 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.MethodsC57BL/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.ResultsAfter 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-γ, 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.ConclusionIn 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. |
| first_indexed | 2024-12-22T10:35:34Z |
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| language | English |
| last_indexed | 2024-12-22T10:35:34Z |
| publishDate | 2021-08-01 |
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| spelling | doaj.art-f2547fe51f594c1bb84f27c0830e3b8f2022-12-21T18:29:13ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-08-011210.3389/fimmu.2021.687919687919Ikzf2 Regulates the Development of ICOS+ Th Cells to Mediate Immune Response in the Spleen of S. japonicum-Infected C57BL/6 MiceShihao Xie0Haixia Wei1Anping Peng2Anqi Xie3Jiajie Li4Chao Fang5Feihu Shi6Quan Yang7He Huang8Hongyan Xie9Xingfei Pan10Xu Tian11Xu Tian12Jun Huang13Jun Huang14Department of Infectious Diseases, Key Laboratory for Major Obsteric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaBiological Resource Center, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaDepartment of Infectious Diseases, Key Laboratory for Major Obsteric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaDepartment of Infectious Diseases, Key Laboratory for Major Obsteric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaDepartment of Infectious Diseases, Key Laboratory for Major Obsteric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaCollege of Pharmacy, Guangzhou Medical University, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaKey Laboratory of Immunology, Sino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou, ChinaBackgroundTh 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.MethodsC57BL/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.ResultsAfter 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-γ, 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.ConclusionIn 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.687919/fullSchistosoma japonicumspleenCD4+ T cellsICOSIkzf2(Helios) |
| spellingShingle | Shihao Xie Haixia Wei Anping Peng Anqi Xie Jiajie Li Chao Fang Feihu Shi Quan Yang He Huang Hongyan Xie Xingfei Pan Xu Tian Xu Tian Jun Huang Jun Huang 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 Schistosoma japonicum spleen CD4+ T cells ICOS Ikzf2(Helios) |
| title | Ikzf2 Regulates the Development of ICOS+ Th Cells to Mediate Immune Response in the Spleen of S. japonicum-Infected C57BL/6 Mice |
| title_full | Ikzf2 Regulates the Development of ICOS+ Th Cells to Mediate Immune Response in the Spleen of S. japonicum-Infected C57BL/6 Mice |
| title_fullStr | Ikzf2 Regulates the Development of ICOS+ Th Cells to Mediate Immune Response in the Spleen of S. japonicum-Infected C57BL/6 Mice |
| title_full_unstemmed | Ikzf2 Regulates the Development of ICOS+ Th Cells to Mediate Immune Response in the Spleen of S. japonicum-Infected C57BL/6 Mice |
| title_short | Ikzf2 Regulates the Development of ICOS+ Th Cells to Mediate Immune Response in the Spleen of S. japonicum-Infected C57BL/6 Mice |
| title_sort | ikzf2 regulates the development of icos th cells to mediate immune response in the spleen of s japonicum infected c57bl 6 mice |
| topic | Schistosoma japonicum spleen CD4+ T cells ICOS Ikzf2(Helios) |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.687919/full |
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