An overview of immune checkpoint therapy in autoimmune diseases

Immune checkpoint receptors are critical regulators of initiation and termination of effective immune responses as well as maintain self-tolerance. Since the successful use of immune checkpoint inhibitors in cancer immunotherapy, they gained huge interest to be used in autoimmune diseases treatment. Indeed, abatacept (CTLA4-Ig), as immune checkpoint inhibitors has made major advancement in the treatment of rheumatoid arthritis patients who have failed to respond to csDMARDs or TNF-α inhibitor. Over the past decade, an increasing number of new immune checkpoints have been detected and lots of investigations are in progress to address their potential as possible targets of effective novel immunotherapy. Here we focus on the biological functions and structures of these immune checkpoints, their pharmacological mechanisms, pathogenesis, therapeutic effects, and their related adverse events. We also discuss the application of agonistic or antagonistic agents targeting co-inhibitory or co-stimulatory checkpoints for the treatment of autoimmune diseases. Furthermore, we summarize previous and recent clinical trials utilizing these immune checkpoints in autoimmune diseases. Obviously, the characterization of such processes might help to develop more effective therapeutic agents in the future.