AIM2-Silenced Dendritic Cells Possess Immunosuppressive Phenotype and Prolong Allograft Survival by Modulating the Th1/Th17/Treg Balance

Abstract

Dendritic cells (DCs) serve a pivotal and diverse role in the modulation of transplant immunity, wherein alterations in their maturation state influence the balance between promoting immunotolerance and exacerbating inflammatory responses. Recent studies have revealed a spectrum of novel mechanisms through which absent in melanoma 2 (AIM2) regulates the functions of immune cells. However, the impact of AIM2 on the regulatory functions of dendritic cells in alloimmunity has not been thoroughly investigated. In this study, we constructed a recombinant adenovirus vector containing AIM2 interference sequences for the transduction of DCs, aiming to suppress AIM2 expression within these cells. Our findings indicate that silencing AIM2 preserved a semi-mature status of DCs upon lipopolysaccharide (LPS) exposure, alongside maintaining reduced levels of pro-inflammatory cytokine secretion and enhanced phagocytic activity. When co-cultured with allogeneic naive T cells, AIM2-silenced DCs demonstrated reduced activation potential of CD4⁺ and CD8⁺ T cells in response to LPS stimulation. The transfusion of AIM2-silenced DCs into recipient mice led to a notable prolongation of graft survival and a decrease in inflammatory cell infiltration within the graft. Furthermore, mice treated with AIM2-silenced DCs exhibited a higher percentage of regulatory T cells in their spleen and abdominal lymph nodes, concomitant with a decrease in the proportions of Th1 and Th17 cell subpopulations. AIM2-silenced DCs exhibit stable immunosuppressive capabilities, offering an effective strategy for alleviating allograft rejection.