Our present study highlighted five genes (USP3, AMFR, HERC1, CC2D2B, and RP11-326C3.7) that may play a pivotal role in the communication between circulating neutrophils, pDC, NKT, and periodontitis, as well as two high-confidence genes (S100A9, S100A12) situated within 1q21.3 as prospective gene targets for regulating circulating neutrophils during periodontitis. Here, CC2D2B is linked to periodontitis.