Checkpoint agonists - immunoregulatory role and its implications in the treatment of psoriasis and psoriatic arthritis.

Psoriasis and psoriatic arthritis are chronic autoimmune diseases characterized by dysregulated immune responses, particularly involving Th17 cells. Immune checkpoint molecules such as programmed death-1 (PD-1) and its ligands (PD-L1/PD-L2) are critical for maintaining immune tolerance. Disruptions in these pathways contribute to psoriatic disease pathogenesis. Notably, immune checkpoint inhibitors used in cancer therapy have been linked to the development of psoriasis or its exacerbation. This highlights the complex role of checkpoint pathways in psoriatic diseases. Thus, immune checkpoint agonists could be a therapeutic strategy aimed at restoring immune balance without widespread immunosuppression. Preclinical studies demonstrate that PD-1 agonists can mitigate inflammation by enhancing inhibitory signaling. Additionally, early-phase clinical trials in autoimmune diseases such as rheumatoid arthritis and ulcerative colitis suggest potential benefits of PD-1 modulation in psoriasis. This review explores immune checkpoint agonists in psoriatic disease as a promising alternative to conventional immunosuppressants by selectively suppressing pathogenic T-cell activity.