In summary, through the in vivo mouse model of P. gingivalis LPS-induced periodontitis and in vitro co-culture system of mandibular BM-MSCs and pre-activated splenic CD4 T cells, we revealed a novel axis of LncRNA SPIRE1/miR-181a-5p/PRLR in regulating the immunomodulatory properties of mandibular BM-MSCs. The gene discussed is SPIRE1; the disease is periodontitis.