Cuenca Lab | Using adjuvant conditioning to shape the immune system

Using adjuvant conditioning to shape the immune system

adjuvant conditioning aria description — Creating a suppressive milieu requires coordination of multiple immunoregulatory cell populations including myeloid derived suppressor cells and T regulatory T cells. These cells either interact with alloimmune responses through the production of suppressive cytokines like IL-10 or through direct cell to cell interactions like PD-L1. This picture describes this complex interplay and what our lab hopes to achieve with adjuvant conditioning.

Through repeated adjuvant administration, termed adjuvant conditioning (AC), our lab is developing a way to shape a transplant recipient’s immune system to be more tolerant to transplanted solid organs to decrease the burden of immunosuppression. One consequence of this may be the development of a suppressive trained immune responses.

Trained immunity is thought to mainly enhance the responsiveness of the innate immune system upon restimulation. Although adjuvants are used to enhance immune responses, we have shown that repeated administration of alum, termed adjuvant conditioning, establishes an immunosuppressive environment that delays allogeneic graft rejection by expanding myeloid-derived suppressor cells (MDSCs) (Ge et al., American Journal of Transplantation 2023). In addition, we have preliminary data that suggests that AC-induced MDSCs suppress antigen specific adaptive responses both in vitro and in vivo, and that the immunosuppression is dependent on NLRP3 and IL-1 signaling. In addition, our studies also suggest that AC can train an immunosuppressive response in MDSCs which demonstrate decreased inflammatory cytokine production and increased immunosuppressive cytokine production on restimulation with inflammatory stimuli. These data suggest that targeting the NLRP3/IL-1 pathway as a new promising strategy to condition transplant recipients and ‘train tolerance’.