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

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.