Preventing Immune Rejection Through Gene Silencing

Dendritic cells (DCs) comprise a family of professional antigen-presenting cells responsible for the induction of primary immune responses. DCs are also important for the induction of immunological tolerance. Recent research has revealed that DC maturation is associated with activation of the NF-κB pathway. RelB, one of the five families of Rel proteins involved in the NF-κB pathway, plays a critical role in coordinating the terminal stages of DC maturation and has the ability to induce optimal Th1 T cell responses. DCs generated from mouse bone marrow can be silenced using siRNA specific for the target gene. Silencing RelB in DCs will result in the generation of immunoregulatory dendritic cells that inhibit allogenic T cell responses. The KLH-specific T cell response should also be inhibited after the RelB siRNA treatment. Furthermore, silencing the RelB gene in DCs can generate regulatory T cells. Administering donor-derived RelB-silencing DCs can prevent allograft rejection in murine heart transplantation.