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Immunol."],"abstract":"<jats:p>T cells contribute to immunotherapy and autoimmune pathogenesis and Langerhans cells (LCs) have a substantial ability to activate T cells. <jats:italic>In vitro<\/jats:italic>-generated monocyte-derived LCs (Mo-LCs) are useful models to study LC function in autoimmune diseases and to test future LC-based immunotherapies. Although dendritic cells (DCs) expressing high levels of Delta-like 4 (DLL4<jats:sup>+<\/jats:sup> DCs), which is a member of the Notch ligand family, have greater ability than DLL4<jats:sup>\u2212<\/jats:sup> DCs to activate T cells, the induction method of human DLL4<jats:sup>+<\/jats:sup> DCs has yet to be determined. The aim of this study is to establish whether Mo-LCs express DLL4 and establish the induction method of antigen presenting cells, which most potently activate T cells, similar to our previously established induction method of human Mo-LCs. We compared the ratios of DLL4 expression and T cell activation via flow cytometry among monocyte-derived cells, which have a greater ability than the resident cells to activate T cells. Here, we discovered that Mo-LCs expressed DLL4, which most potently activated T cells among monocyte-derived cells, and that Mo-LCs and DLL4 expression were induced by DLL4, granulocyte macrophage colony-stimulating factor, and transforming growth factor-\u03b21. Additionally, peptidoglycan was required for DLL4 expression, whereas interleukin-4 repressed it. These findings provide insights into the roles of DLL4-expressing cells such as DLL4<jats:sup>+<\/jats:sup> Mo-LCs in human diseases, which will assist with the development of more effective therapeutic strategies in the future.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1532620","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T07:09:14Z","timestamp":1739430554000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Monocyte-derived Langerhans cells express Delta-like 4 induced by peptidoglycan and interleukin-4 mediated 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