State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
J Dent Res. 2024 Oct;103(11):1130-1140. doi: 10.1177/00220345241271078. Epub 2024 Sep 18.
N6,2'-O-dimethyladenosine (mAm), 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 mAm methyltransferase phosphorylated CTD interacting factor 1 (PCIF1) attenuates periodontal inflammation in whole-body and myeloid lineage-specific knockout mouse models. deletion inhibits macrophage phagocytosis and migration through mAm-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 mAm modification in governing macrophage responses and periodontal inflammation.
N6,2'-O-二甲基腺苷（mAm）是真核生物帽状 mRNA 中的一种常见 mRNA 修饰物，在细胞功能和疾病进展中发挥关键作用。然而，其在宿主炎症中的作用仍不清楚。在这里，我们证明 mAm 甲基转移酶磷酸化 CTD 相互作用因子 1（PCIF1）的缺失减轻了全身性和髓系特异性敲除小鼠模型中的牙周炎症。缺失抑制了巨噬细胞的吞噬和迁移，通过 mAm-Csf1r 信号。此外，集落刺激因子-1 受体（CSF1R）被鉴定为治疗牙周炎的潜在靶点。因此，我们揭示了 PCIF1 介导的 mAm 修饰在调节巨噬细胞反应和牙周炎症中的一个以前未被认识的作用。
