Work

Investigating the mechanistic basis for dendritic cell-intrinsic AIMp1 regulation of dendritic cell maturation and anti-tumor immunity 4111

Year: 2025

Type: article

Abstract: Description Dendritic cells (DC) are the only antigen presenting cell subset capable of both initiating adaptive immunity and driving downstream immune polarization. As such, the importance of DCs for anti-tumor immunity is paramount, but tumor-associated DCs are often dysfunctional and fail to induce effective immune responses. Therefore, gaining a greater understanding of DC-intrinsic functions that drive favorable tumor immunity is critical for developing more effective cancer immunotherapeutics. Recent work has implicated the function of an intracellular protein complex—called the multi-aminoacyl tRNA synthetase complex (mARS)—in regulating tumor immunity. Within DCs, a mARS subunit, called AIMp1, is dispensable for normal DC hematopoiesis but is required during DC maturation to facilitate effective anti-tumor immunity. We therefore investigated the specific DC-intrinsic signaling events mediated by AIMp1 within maturing DCs. Early in the maturation process, we found a novel protein-protein interaction between AIMp1 and NMNAT1, indicating AIMp1 may regulate cellular signaling via intracellular NAD(H) homeostasis. Additionally, nearly all AIMp1 molecules were bound within mARS in steady-state immature DCs. But after stimulation, a pool of soluble intracellular AIMp1 forms, suggesting AIMp1’s role in DC signaling is dynamically regulated during maturation. In conclusion, this work revealed a novel mechanistic and stage-specific role for AIMp1 as a positive regulator of DC maturation. Funding Sources NIH 5R01AI153326 Topic Categories Antigen and Dendritic Cell Processing, Presentation, and Biology (AGDC)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.1832