Role of PRDM1 in natural killer cells

PRDM1, a pivotal transcription factor within the PRDM family, serves as a critical regulator of Natural Killer (NK) cell biology. Initially identified as PRDⅠ-BF1/BLIMP-1, PRDM1 is characterized by a conserved PR domain and multiple zinc finger motifs, which enable its sequence-specific DNA binding and protein-protein interactions. Its expression in NK cells is tightly regulated by upstream transcription factors as well as cytokine signaling. Mechanistically, PRDM1 exerts transcriptional repression through several coordinated mechanisms: direct DNA binding to target gene promoters, induction of chromatin remodeling via histone modification, and recruitment of co-repressors like Groucho and histone deacetylases, thereby orchestrating NK cell maturation and effector functions. These direct molecular functions of PRDM1 have been characterized largely in vitro. In vivo, PRDM1 also shapes NK cell maturation and effector functions; however, phenotypes observed in knockout mice reflect the integrated outcome of PRDM1 loss throughout NK cell development, differentiation and homeostasis, in which compensatory mechanisms may operate, and therefore cannot be attributed solely to the direct cell-intrinsic functions of PRDM1. This review synthesizes the historical evolution of PRDM1 research, elucidates its structural characteristics, and details its gene regulatory mechanisms. A comprehensive understanding of the PRDM1 regulatory network offers profound insights into NK cell biology and highlights potential therapeutic targets for immune-related disorders such as autoimmune diseases and cancer immunotherapy.