N6,2′-O-dimethyladenosine (m6Am), 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 m6Am 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 m6Am-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 m6Am modification in governing macrophage responses and periodontal inflammation.

中文翻译：

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m6Am 甲基转移酶 PCIF1 调节牙周炎


N6,2′-O-二甲基腺苷 （m6Am） 是真核加帽 mRNA 中常见的 mRNA 修饰，在细胞功能和疾病进展中起着关键作用。然而，它与宿主炎症的参与仍然难以捉摸。在这里，我们证明 m6Am 甲基转移酶磷酸化 CTD 相互作用因子 1 （PCIF1） 的缺失减轻了全身和骨髓谱系特异性敲除小鼠模型中的牙周炎。Pcif1 缺失通过 m6Am-Csf1r 信号传导抑制巨噬细胞吞噬和迁移。此外，集落刺激因子-1 受体 （CSF1R） 被确定为治疗牙周炎的潜在靶点。因此，我们揭示了 PCIF1 介导的 m6Am 修饰在控制巨噬细胞反应和牙周炎中以前未被认识的作用。