Immunological cross-talk between periodontitis and systemic lupus erythematosus: the role of T–B cell dysregulation in the shared pathogenic network

Abstract

Periodontitis and systemic lupus erythematosus (SLE) exhibit overlapping immunopathological features characterized by dysregulated adaptive immune responses. Emerging evidence suggests that aberrant T–B cell crosstalk represents a potential immunological link between chronic oral inflammation and systemic autoimmunity. Persistent periodontal inflammation promotes the release of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), leading to dendritic cell activation, neutrophil extracellular trap (NET) formation, and sustained immune stimulation. These signals may facilitate abnormal germinal center responses through enhanced Tfh–B cell interactions and increased BAFF and IL-21 signaling, thereby amplifying B-cell activation, plasma-cell differentiation, and antibody production. Conversely, SLE-associated systemic immune dysregulation may aggravate periodontal inflammation, suggesting a potentially bidirectional interaction between oral and systemic immunity. However, most available evidence has been obtained from separate studies of periodontitis and SLE and does not establish a shared causal pathway between the two diseases. In this review, we summarize current evidence supporting the role of T–B cell dysregulation as a potential immunological link between periodontitis and SLE. We further discuss candidate mechanisms involving dendritic cells, NETs, BAFF, IL-21, and germinal center reactions, as well as their therapeutic implications. Elucidating the oral–systemic immune axis may provide novel insights into integrated immunomodulatory strategies for autoimmune diseases.