Dataset Information

Ikzf2 Regulates the Development of ICOS⁺ Th Cells to Mediate Immune Response in the Spleen of S. japonicum-Infected C57BL/6 Mice.

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.

SUBMITTER: Xie S

PROVIDER: S-EPMC8406689 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Determining the molecular events induced in the spleen during schistosome infection is an essential step in better understanding the immunopathogenesis of schistosomiasis and the mechanisms by which schistosomes modulate the host immune response. The present study defines the transcriptional and cellular events occurring in the murine spleen during the progression of Schistosoma japonicum infection. Additionally, we compared and contrasted these results with those we have previously reported for the liver. Microarray analysis combined with flow cytometry and histochemistry demonstrated that transcriptional changes occurring in the spleen were closely related to changes in cellular composition. Additionally, the presence of alternatively activated macrophages, as indicated by up-regulation of Chi3l3 and Chi3l4 and expansion of F4/80+ macrophages, together with enhanced expression of the immunoregulatory genes ANXA1 and CAMP suggests the spleen may be an important site for the control of S. japonicum-induced immune responses. The most striking difference between the transcriptional profiles of the infected liver and spleen was the contrasting expression of chemokines and cell adhesion molecules. Lymphocyte chemokines including the homeostatic chemokines, CXCL13, CCL19 and CCL21, were significantly down-regulated in the spleen but up-regulated in the liver. Eosinophil (CCL11, CCL24), neutrophil (CXCL1) and monocyte (CXCL14, CCL12) chemokines and the cell adhesion molecules VCAM1, NCAM1, PECAM1 were up-regulated in the liver but unchanged in the spleen. Chemokines up-regulated in both organs were expressed at significantly higher levels in the liver. Co-ordinated expression of these genes probably contributes to the development of a chemotactic signalling gradient that promotes recruitment of effector cells to the liver, thereby facilitating the development of hepatic granulomas and fibrosis. Together these data provide, for the first time, a comprehensive overview of the molecular events occurring in the spleen during schistosomiasis and will substantially further our understanding of the local and systemic mechanisms driving the immunopathogenesis of this disease.

Project description:Determining the molecular events induced in the spleen during schistosome infection is an essential step in better understanding the immunopathogenesis of schistosomiasis and the mechanisms by which schistosomes modulate the host immune response. The present study defines the transcriptional and cellular events occurring in the murine spleen during the progression of Schistosoma japonicum infection. Additionally, we compared and contrasted these results with those we have previously reported for the liver. Microarray analysis combined with flow cytometry and histochemistry demonstrated that transcriptional changes occurring in the spleen were closely related to changes in cellular composition. Additionally, the presence of alternatively activated macrophages, as indicated by up-regulation of Chi3l3 and Chi3l4 and expansion of F4/80(+) macrophages, together with enhanced expression of the immunoregulatory genes ANXA1 and CAMP suggests the spleen may be an important site for the control of S. japonicum-induced immune responses. The most striking difference between the transcriptional profiles of the infected liver and spleen was the contrasting expression of chemokines and cell adhesion molecules. Lymphocyte chemokines, including the homeostatic chemokines CXCL13, CCL19 and CCL21, were significantly down-regulated in the spleen but up-regulated in the liver. Eosinophil (CCL11, CCL24), neutrophil (CXCL1) and monocyte (CXCL14, CCL12) chemokines and the cell adhesion molecules VCAM1, NCAM1, PECAM1 were up-regulated in the liver but unchanged in the spleen. Chemokines up-regulated in both organs were expressed at significantly higher levels in the liver. Co-ordinated expression of these genes probably contributes to the development of a chemotactic signalling gradient that promotes recruitment of effector cells to the liver, thereby facilitating the development of hepatic granulomas and fibrosis. Together these data provide, for the first time, a comprehensive overview of the molecular events occurring in the spleen during schistosomiasis and will substantially further our understanding of the local and systemic mechanisms driving the immunopathogenesis of this disease.

Dataset Information

Ikzf2 Regulates the Development of ICOS⁺ Th Cells to Mediate Immune Response in the Spleen of S. japonicum-Infected C57BL/6 Mice.

Background

Methods

Results

Conclusion

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OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

Ikzf2 Regulates the Development of ICOS+ Th Cells to Mediate Immune Response in the Spleen of S. japonicum-Infected C57BL/6 Mice.

Background

Methods

Results

Conclusion

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Ikzf2 Regulates the Development of ICOS⁺ Th Cells to Mediate Immune Response in the Spleen of S. japonicum-Infected C57BL/6 Mice.