{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:09:26Z","timestamp":1774656566727,"version":"3.50.1"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T00:00:00Z","timestamp":1628726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Th cells (helper T cells) have multiple functions in <jats:italic>Schistosoma japonicum<\/jats:italic> (<jats:italic>S. japonicum<\/jats:italic>) 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<jats:sup>+<\/jats:sup> Th cells in the spleen of <jats:italic>S. japonicum<\/jats:italic>-infected C57BL\/6 mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>C57BL\/6 mice were infected with cercariae of <jats:italic>S. japonicum<\/jats:italic> through the abdomen. The expression of ICOS, activation markers, and the cytokine production on CD4<jats:sup>+<\/jats:sup> ICOS<jats:sup>+<\/jats:sup> Th cells were detected by flow cytometry (FCM) and quantitative real-time PCR (qRT-PCR). Moreover, the differentially expressed gene data of ICOS<jats:sup>+<\/jats:sup> and ICOS<jats:sup>\u2212<\/jats:sup> 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After <jats:italic>S. japonicum<\/jats:italic> infection, the expression of ICOS molecules gradually increased in splenic lymphocytes, especially in Th cells (<jats:italic>P<\/jats:italic> &amp;lt; 0.01). Compared with ICOS<jats:sup>\u2212<\/jats:sup> Th cells, more ICOS<jats:sup>+<\/jats:sup> Th cells expressed CD69, CD25, CXCR5, and CD40L (<jats:italic>P<\/jats:italic>\u00a0&amp;lt; 0.05), while less of them expressed CD62L (<jats:italic>P<\/jats:italic> &amp;lt; 0.05). Also, ICOS<jats:sup>+<\/jats:sup> Th cells expressed more cytokines, such as IFN-\u03b3, IL-4, IL-10, IL-2, and IL-21 (<jats:italic>P<\/jats:italic> &amp;lt; 0.05). RNA sequencing results showed that many transcription factors were increased significantly in ICOS<jats:sup>+<\/jats:sup> Th cells, especially Ikzf2 (<jats:italic>P<\/jats:italic> &amp;lt; 0.05). And then, the expression of Ikzf2 was verified to be significantly increased and mainly located in the nuclear of ICOS<jats:sup>+<\/jats:sup> Th cells. Finally, ChIP experiments and dual-luciferase reporter assay confirmed that Ikzf2 could directly bind to the ICOS promoter in Th cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In this study, ICOS<jats:sup>+<\/jats:sup> Th cells were found to play an important role in <jats:italic>S. japonicum<\/jats:italic> 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 <jats:italic>S. japonicum<\/jats:italic>-infected C57BL\/6 mice.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2021.687919","type":"journal-article","created":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T10:09:25Z","timestamp":1628762965000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Ikzf2 Regulates the Development of ICOS+ Th Cells to Mediate Immune Response in the Spleen of S. japonicum-Infected C57BL\/6 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