Roles of Notch and NF-kB signaling in allogeneic responses

Abstract

The induction of robust allograft tolerance is the ultimate goal for clinical transplantation. Although studies have identified that dendritic cells (DCs) are important for induction of antigen-specific tolerance, the requirements for generating tolerogenic DCs are yet to be elucidated. Recently, it has been demonstrated the modulation of two signaling pathways, Notch and nuclear factor KB (NF-KB) can render DCs tolerogenic. The studies documented here examine (1) whether immature DCs over-expressing Notch-related molecules (Jagged-I, Delta-like-I (Dll-I), Lunatic Fringe (Ung) , and Manic Fringe (Mfng)) act as immunoregulatory DCs and promote allograft survival; and (2) whether DCs deficient in NF-KB signaling inhibit the alloreactive T cell response and promote allograft survival ... Although the potential for Notch signaling to promote alloantigen-specific tolerance remains unresolved, these studies suggest that inhibition of NF-KB signaling in DCs represent a potential approach for promoting allograft survival.