m⁶Am Methyltransferase PCIF1 Regulates Periodontal Inflammation

N6,2′-O-dimethyladenosine (m 6 Am), a common mRNA modification in eukaryotic capped mRNAs, plays a pivotal role in cellular functions and disease progression. However, its involvement in host inflammation remains elusive. Here, we demonstrate that loss of m 6 Am methyltransferase phosphorylated CTD interacting factor 1 (PCIF1) attenuates periodontal inflammation in whole-body and myeloid lineage–specific knockout mouse models. Pcif1 deletion inhibits macrophage phagocytosis and migration through m 6 Am-Csf1r signaling. In addition, colony-stimulating factor-1 receptor (CSF1R) is identified as a potential target for the treatment of periodontitis. We thus reveal a previously unrecognized role for PCIF1-mediated m 6 Am modification in governing macrophage responses and periodontal inflammation.