Porphyromonas gingivalis promotes T-cell homing via the NF-κB/CXCR3 signaling pathway in experimental autoimmune encephalomyelitis

Background Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS); experimental autoimmune encephalomyelitis (EAE) is its model. Periodontitis involving Porphyromonas gingivalis (P. gingivalis) has been linked to MS and shown to exacerbate EAE, but mechanisms remain unclear.Methods Mice were randomized into four groups (n = 8): control, periodontitis only, EAE only, and EAE with periodontitis. Neurological deficits were assessed daily. Spinal CD4⁺ and CD4⁺CXCR3⁺ T-cell infiltration and NF-κB activation were evaluated by immunofluorescence. Peripheral CD4⁺CXCR3⁺ T-cell frequencies were quantified by flow cytometry. T-cell chemotaxis and CXCR3 expression were assessed.Results P. gingivalis -induced periodontitis significantly aggravated EAE neurological deficits from days 15 to 21. RNA-seq re-analysis revealed NF-κB signaling enrichment and Cxcr3, Cxcl10, and Nfkb upregulation. In vivo, P. gingivalis increased peripheral CD4⁺CXCR3⁺ T cells, spinal CD4⁺ and CD4⁺CXCR3⁺ T-cell infiltration, and NF-κB activation. In vitro, P. gingivalis promoted CXCR3-dependent T-cell migration. NF-κB inhibition attenuated P. gingivalis -induced NF-κB activation, downregulated CXCR3 expression, and reduced CD4⁺CXCR3⁺ T cells.Conclusion P. gingivalis -induced periodontitis aggravates EAE clinical severity, potentially involving NF-κB activation, CXCR3 upregulation on peripheral T cells and enhanced T-cell migratory capacity and infiltration into the CNS. These findings identify a potential mechanistic link between periodontitis and MS pathogenesis.