Tolerogenic dendritic cells generated by RelB silencing using shRNA prevent acute rejection

Cell Immunol. 2012;274(1-2):12-8. doi: 10.1016/j.cellimm.2012.02.012. Epub 2012 Mar 14.

Abstract

It is well known that adoptive transfer of donor-derived tolerogenic dendritic cells (DCs) helps to induce immune tolerance. RelB, one of NF-κB subunits, is a critical element involved in DC maturation. In the present study, our results showed tolerogenic DCs could be acquired via silencing RelB using small interfering RNA. Compared with imDCs, the tolerogenic DCs had more potent ability to inhibit mixed lymphocyte reaction (MLR) and down-regulate Th1 cytokines and prompt the production of Th2 cytokines. They both mediated immune tolerance via the increased of T cell apoptosis and generation of regulatory T cells. Administration of donor-derived tolerogenic DCs significantly prevented the allograft rejection and prolonged the survival time in a murine heart transplantation model. Our results demonstrate donor-derived, RelB-shRNA induced tolerogenic DCs can significantly induce immune tolerance in vitro and in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Apoptosis / immunology
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Dendritic Cells / immunology*
  • Dendritic Cells / transplantation*
  • Graft Rejection / genetics
  • Graft Rejection / immunology*
  • Graft Survival / immunology
  • Heart Transplantation / immunology
  • Immune Tolerance*
  • Lymphocyte Culture Test, Mixed
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • RNA Interference*
  • RNA, Small Interfering
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th2 Cells / metabolism
  • Transcription Factor RelB / genetics*

Substances

  • Cytokines
  • RNA, Small Interfering
  • Relb protein, mouse
  • Transcription Factor RelB