Citrullinated antigen-specific regulatory B cells and regulatory T cells

Citrullinated antigen-specific regulatory B cells (Bregs) and regulatory T cells (Tregs) are specialized immune cell subsets that play a pivotal role in maintaining peripheral tolerance to post-translationally modified self-proteins (Law et al., 2020, JCI Insight). In the context of Rheumatoid Arthritis (RA), the breakdown of tolerance to citrullinated antigens leads to the development of anti-citrullinated protein antibodies (ACPAs) and chronic joint inflammation (Sonderen et al., 2019, Nature Communications). These regulatory cells function by secreting anti-inflammatory cytokines such as IL-10 and TGF-beta, and by directly suppressing the activity of pathogenic effector T cells and B cells. Therapeutic interventions, such as tolerogenic vaccines like DEN-181, are designed to selectively induce or expand these specific regulatory populations to restore immune balance (Benham et al., 2015, Science Translational Medicine). Unlike broad-spectrum immunosuppressants, targeting these antigen-specific cells aims to provide a precise re-education of the immune system, potentially leading to drug-free remission. The success of such therapies is often monitored through the quantification of citrulline-specific T-cell receptors and the reduction of ACPA titers in patient serum. These cells are considered a cellular target rather than a single molecular target, as the therapy aims to modulate the entire population's frequency and function. Safety concerns include the theoretical risk of paradoxical immune activation or epitope spreading, where the immune response expands to other self-antigens. Current research focuses on identifying the most relevant citrullinated epitopes to include in these tolerogenic formulations. Overall, these cells represent a frontier in precision medicine for autoimmune diseases.

Other names

Citrullinated peptide-specific regulatory T cellsCitrullinated peptide-specific regulatory B cellsACPA-specific regulatory cellsCit-specific TregsCit-specific Bregs

Induction of antigen-specific immune tolerance by promoting the expansion and activation of regulatory T and B cell subsets that recognize citrullinated self-antigens.