A narrative review of PD-1 and autoimmune diseases

Background: This review summarizes current findings and biological functions of programmed cell death protein 1 (PD-1) in several major autoimmune diseases and their potential application to clinical management and future research. Autoimmune diseases afflict approximately 3% of the world's population. Although the etiology and pathogenesis of these diseases have not yet been completely elucidated, in recent year new molecular pathways of PD-1 (CD279) responsible for regulating tolerance and autoimmunity have been discovered, and the role of PD-1 in autoimmune diseases has been gradually recognized and reported. Methods: Information used to write this paper was collected from searches of computerized databases. The main search terms are PD-1 and its related contents, and most of the references come from related studies published in the past 10 years. Results: In this article, because of the emerging evidence for a close relationship between PD-1 and autoimmune diseases, we describe detailed findings and roles of PD-1 in four types of autoimmune diseases that include rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS) and type 1 diabetes (T1D). Conclusions: An increase of PD-1+ T cell populations found in both RA and SLE patients, and in Treg cell subsets overexpressing PD-1 in MS patients, are finding which may represent dysfunctional Treg subpopulations. The development of TID is known to occur as a side effect of anti-PD-1 therapy. In this article, we found that cells expressing PD-1 may paradoxically also promote the disease in autoimmune diseases, which is different from the traditional inhibitory role attributed to PD-1. Therefore, the role of PD-1 in autoimmune diseases is quite promising and warrants a further in-depth research.