title: Development of Stem Cell-derived Antigen-specific Regulatory T Cells Against Autoimmunity.
abstract: Autoimmune diseases arise due to the loss of immunological self-tolerance. Regulatory T cells (Tregs) are important mediators of immunologic self-tolerance. Tregs represent about 5 - 10% of the mature CD4+T cell subpopulation in mice and humans, with about 1 - 2% of those Tregs circulating in the peripheral blood. Induced pluripotent stem cells (iPSCs) can be differentiated into functional Tregs, which have a potential to be used for cell-based therapies of autoimmune diseases. Here, we present a method to develop antigen (Ag)-specific Tregs from iPSCs (i.e., iPSC-Tregs). The method is based on incorporating the transcription factor FoxP3 and an Ag-specific T cell receptor (TCR) into iPSCs and then differentiating on OP9 stromal cells expressing Notch ligands delta-like (DL) 1 and DL4. Following in vitro differentiation, the iPSC-Tregs express CD4, CD8, CD3, CD25, FoxP3, and Ag-specific TCR and are able to respond to Ag stimulation. This method has been successfully applied to cell-based therapy of autoimmune arthritis in a murine model. Adoptive transfer of these Ag-specific iPSC-Tregs into Ag-induced arthritis (AIA)-bearing mice has the ability to reduce joint inflammation and swelling and to prevent bone loss.
authors.affiliation: Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Haque
authors.affiliation: Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine.
authors.forename: Kristin
authors.initials: K
authors.lastname: Fino
authors.affiliation: Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine.
authors.forename: Praneet
authors.initials: P
authors.lastname: Sandhu
authors.affiliation: Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine; jus35@psu.edu.
authors.forename: Jianxun
authors.initials: J
authors.lastname: Song
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001168:Arthritis / Q000628:therapy; D015551:Autoimmunity; D051858:Forkhead Transcription Factors; D006801:Humans; D007108:Immune Tolerance; D051379:Mice; D013234:Stem Cells; D050378:T-Lymphocytes, Regulatory
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors