Abstract
Autoimmune diseases, such as multiple sclerosis and type-1 diabetes, are the outcomes of a failure of immune tolerance. Immune tolerance is sustained through interplays between two inter-dependent clusters of immune activities: immune stimulation and immune regulation. The mechanisms of immune regulation are exploited as therapeutic targets for the treatment of autoimmune diseases. One of these mechanisms is immune checkpoints (ICPs). The roles of ICPs in maintaining immune tolerance and hence suppressing autoimmunity were revealed in animal models and validated by the clinical successes of ICP-targeted therapeutics for autoimmune diseases. Recently, these roles were highlighted by the clinical discovery that the blockade of ICPs causes autoimmune disorders. Given the crucial roles of ICPs in immune tolerance, it is plausible to leverage ICPs as a group of therapeutic targets to restore immune tolerance and treat autoimmune diseases. In this review, we first summarize working mechanisms of ICPs, particularly those that have been utilized for therapeutic development. Then, we recount the agents and approaches that were developed to target ICPs and treat autoimmune disorders. These agents take forms of fusion proteins, antibodies, nucleic acids, and cells. We also review and discuss safety information for these therapeutics. We wrap up this review by providing prospects for the development of ICP-targeting therapeutics. In summary, the ever-increasing studies and results of ICP-targeting of therapeutics underscore their tremendous potential to become a powerful class of medicine for autoimmune diseases.
Highlights
The immune system is powerful and versatile in protecting the body: it neutralizes invading pathogens and toxins, detects and destroys infected and malignant cells, and orchestrates the recovery of compromised tissues
These results unambiguously demonstrate the central role of PD1 positive cells in these autoimmune diseases
Evidences from preclinical studies and clinical trials have shown that an abolishment or a blockade of immune checkpoints (ICPs) leads to the loss of immune tolerance and autoimmune disorders
Summary
The immune system is powerful and versatile in protecting the body: it neutralizes invading pathogens and toxins, detects and destroys infected and malignant cells, and orchestrates the recovery of compromised tissues. Immunostasis is achieved and maintained through the competition and interplays between two clusters of activities, immune stimulation and immune regulation. The failure of immune tolerance, either due to inherited genetic deficiencies or exogeneous stimulants, is the fundamental reason for autoimmune disorders including type 1 diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis (RA), and so on. These diseases affect approximately 12.5% of world population [2]. The main immune activation and inhibition implications of ICPs are illustrated with the representative cell types. It is noteworthy that the receptors and ligands may be expressed by additional cell types. The functional implications of ICPs are not limited to what are illustrated here
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
