Immune-regulatory mechanisms in systemic autoimmune and rheumatic diseases.

Systemic autoimmune and rheumatic diseases (SAIRDs) are thought to develop due to the failure of autoimmune regulation and tolerance. Current therapies, such as biologics, have improved the clinical results of SAIRDs; however, they are not curative treatments. Recently, new discoveries have been made in immune tolerance and inflammation, such as tolerogenic dendritic cells, regulatory T and B cells, Th 17 cells, inflammatory and tolerogenic cytokines, and intracellular signaling pathways. They lay the foundation for the next generation of the therapies beyond the currently used biologic therapies. New drugs should target the core processes involved in disease mechanisms with the aim to attain complete cure combined with safety and low costs compared to the biologic agents. Re-establishment of autoimmune regulation and tolerance in SAIRDs by the end of the current decade should be the final and realistic target.