iScience. 2025 May 13;28(6):112653. doi: 10.1016/j.isci.2025.112653. eCollection 2025 Jun 20.
ABSTRACT
Although adjuvants typically enhance immune responses, we show that repeated alum administration-termed adjuvant conditioning (AC)-induces an immunosuppressive environment that delays allogeneic graft rejection by expanding myeloid-derived suppressor cells (MDSCs). AC-induced MDSCs suppress antigen-specific adaptive responses both in vitro and in vivo, a process dependent on NLRP3 and IL-1 signaling. Allogeneic pancreatic islets transplanted into AC-treated NLRP3-/- mice are not protected, confirming the necessity of NLRP3. Moreover, AC-induced MDSCs cultured with LPS exhibit reduced pro-inflammatory and increased immunosuppressive cytokine production. Similarly, prolonged alum exposure blunts inflammatory cytokine production in human cells. Together, these findings reveal that AC establishes an immunosuppressive milieu via the NLRP3/IL-1 axis. This work suggests that targeting this pathway could promote allograft tolerance in transplant recipients.
PMID:40530419 | PMC:PMC12173022 | DOI:10.1016/j.isci.2025.112653
