Programming of induced pluripotent stem cells into regulatory T cell for arthritis prevention (107.6) Academic Article uri icon

abstract

  • Abstract Forkhead box p3 (FoxP3)-expressing regulatory T cells (Tregs) are involved in the regulation of central immune response and important for maintenance of peripheral immune response. Ectopic expression of FoxP3 conveys Treg phenotype to CD4+ T cells, lending the cells to therapeutic use in the prevention of autoimmune diseases. Previously we reported that induced pluripotent stem (iPS) cells have the capacity to develop into T cells. However, the potential of iPS cells differentiate into functional Tregs are not clear. In this study, we used retrovirus-mediated transduction to introduce mouse iPS cells with the FoxP3 gene and co-cultured the cells with the OP9 cells expressing the Notch ligand Delta like 1 (DL1) protein to induce Treg differentiation. In addition, we used a murine disease model to determine the role of iPS cell-derived Tregs in the treatment of arthritis. We found iPS cells-derived T cells expressed CTLA-4, CD25, and FoxP3 after three-week differentiation both in vitro and in vivo, and were able to secrete cytokines (e.g., IL-10). In addition, adoptive transfer of iPS cell-derived Tregs strongly suppressed arthritis development in the murine model of arthritis induced by collagen. These results indicate that iPS cells can differentiate into functional Tregs. The data suggest a potential novel approach to generate therapeutic Tregs from iPS cells for the treatment of autoimmune diseases Keywords: stem cells, regulatory T cells, FoxP3, T cell differentiation

published proceedings

  • The Journal of Immunology

author list (cited authors)

  • Haque, R., Lei, F., & Song, J.

citation count

  • 0

publication date

  • April 2011