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

Abstract

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.