Inflamm Res. 2026 Apr 1;75(1):75. doi: 10.1007/s00011-026-02217-6.
ABSTRACT
BACKGROUND: In recent decades, the prevalence of allergic diseases globally has increased markedly. This underscores the necessity for a deeper understanding of the immunoregulatory networks that govern hypersensitivity responses. Controlling the balance between T cell activation, tolerance, and immune-mediated tissue damage through inhibitory signaling mechanisms is a key part of maintaining immune homeostasis. The PD-1/PD-L1 and PD-L2 signaling pathways are very important for this. This checkpoint has been well studied in cancer and chronic infections, but its role in allergic diseases is complex and context-dependent.
FINDINGS: PD-L1 and PD-L2 have different effects on the immune system. PD-L1 mostly lowers type 1 immunity and raises type 2 immunity, while PD-L2 mostly promotes type 1 polarization and limits type 2 inflammation. This review goes beyond the well-known asthma model to critically examine new evidence suggesting that the PD-1 pathway may be involved in a wide range of allergic disorders. We integrate recent discoveries from allergic rhinitis, conjunctivitis, dermatological disorders, food allergies, and anaphylaxis, emphasizing how the tissue microenvironment, cellular origin, and disease stage collectively influence whether PD-1 signaling facilitates or inhibits allergic inflammation. By analyzing contradictory findings and identifying gaps in knowledge, we present an advanced model of PD-1 function in allergy.
CONCLUSION: We evaluate the therapeutic possibilities and associated risks of targeting this checkpoint for immunomodulation. In recent decades, the prevalence of allergic diseases globally has increased markedly. This underscores the necessity for a deeper understanding of the immunoregulatory networks that govern hypersensitivity responses. Controlling the balance between T cell activation, tolerance, and immune-mediated tissue damage through inhibitory signaling mechanisms is a key part of maintaining immune homeostasis. The PD-1/PD-L1 and PD-L2 signaling pathways are very important for this. This checkpoint has been well studied in cancer and chronic infections, but its role in allergic diseases is complex and context-dependent. PD-L1 and PD-L2 have different effects on the immune system. PD-L1 mostly lowers type 1 immunity and raises type 2 immunity, while PD-L2 mostly promotes type 1 polarization and limits type 2 inflammation. This review goes beyond the well-known asthma model to critically examine new evidence suggesting that the PD-1 pathway may be involved in a wide range of allergic disorders. We integrate recent discoveries from allergic rhinitis, conjunctivitis, dermatological disorders, food allergies, and anaphylaxis, emphasizing how the tissue microenvironment, cellular origin, and disease stage collectively influence whether PD-1 signaling facilitates or inhibits allergic inflammation. By analyzing contradictory findings and identifying gaps in knowledge, we present an advanced model of PD-1 function in allergy and evaluate the therapeutic possibilities and associated risks of targeting this checkpoint for immunomodulation.
PMID:41917459 | DOI:10.1007/s00011-026-02217-6
