PD-1/PD-L and autoimmunity: A growing relationship

Programmed death 1 (PD-1) and its ligands, namely PD-L1 and PD-L2, are one of the key factors responsible for inhibitory T cell signaling, mediating the mechanisms of tolerance and providing immune homeostasis. Mounting evidence demonstrates that impaired PD-1:PD-L function plays an important role in a variety of autoimmune diseases such as Type 1 diabetes (T1D), encephalomyelitis, inflammatory bowel diseases (IBD), Rheumatoid Arthritis (RA), autoimmune hepatitis (AIH), Behcet's disease (BD), myasthenia gravis (MG), autoimmune uveitis (AU), Sjögren's syndrome (SjS), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), myocarditis, and ankylosing spondylitis (AS). By investigating the candidate genes, genome-wide association studies, and identification of single nucleotide polymorphisms (SNPs) in PD-1 gene in humans, it has been shown that there is a higher risk in relevant genetic associations with developing autoimmune diseases in certain ethnic groups. In this review we have tried to present a comprehensive role of PD-1:PD-L in all recently studied autoimmune diseases.