Insights into the complexities of Citrullination: From immune regulation to autoimmune disease

Citrullination, a post-translational modification that changes arginine to citrulline in proteins, is vital for immune response modulation and cell signaling. Catalyzed by peptidyl arginine deiminases (PADs), citrullination is linked to various diseases, particularly autoimmune disorders like rheumatoid arthritis (RA). Citrullinated proteins can trigger the production of anti-citrullinated protein antibodies (ACPAs), included in RA classification criteria. The immune response to citrullination involves both innate and adaptive immunity, affecting monocytes/macrophages, neutrophils, dendritic cells, natural killer cells, B cells, and T cells. Citrullination contributes to disease development in RA and other conditions such as multiple sclerosis, sepsis, and cancer. Therapeutic strategies targeting citrullination and its effects are being explored, including B cell depletion therapies, T cell-directed approaches, PAD inhibitors, and citrullinated peptide-based vaccines. Understanding the interplay between citrullination and the immune system may lead to novel diagnostic tools and targeted therapies for autoimmune diseases and beyond.