Ikzf2 Regulates the Development of ICOS+ Th Cells to Mediate Immune Response in the Spleen of S. japonicum-Infected C57BL/6 Mice.
Front Immunol
; 12: 687919, 2021.
Article
em En
| MEDLINE
| ID: mdl-34475870
ABSTRACT
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-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.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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Schistosoma japonicum
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Baço
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Esquistossomose Japônica
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Ativação Linfocitária
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Linfócitos T Auxiliares-Indutores
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Fator de Transcrição Ikaros
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Proteína Coestimuladora de Linfócitos T Induzíveis
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article