Harnessing Newton's third-law paradigm to treat autoimmune diseases and chronic inflammations

It paradoxically seems counter-intuitive to consider treatments that activate the immune systems as a method to treat autoimmune diseases and chronic inflammations when these inflammatory conditions are themselves manifested by dysregulated activations of the immune responses. However, according to Newton's Third-Law of fundamental physics which formally states "For every action, there is an equal and opposite reaction", it can be reasonably argued that "For every activated pro-inflammatory response, there is an opposite and intrinsic anti-inflammatory response to follow." Therefore, harnessing these intrinsic self-regulated negative-feedbacks of anti-inflammatory and tolerogenic responses by activating the immune systems represents a novel therapeutic paradigm.

This review endeavoured to examine and discuss the current clinical and experimental evidences and therapeutic potentials of activating the innate and adaptive immune systems via their classical cell receptors, namely Toll-like receptors (TLRs), T-cell receptors (TCRs), and B cell receptors (BCRs), to modulate and suppress pathogenic inflammations.

The evidence presented in this review illustrated the therapeutic potentials and the caveats of  recent approaches and advances in harnessing this unorthodox therapeutic paradigm in the treatments of autoimmune diseases, allergic and chronic inflammations. It highlighted the promising potentials of targeting BCR-activated tolergenic responses as a new approach in this new therapeutic paradigm.