Blockade of PD-L1 accelerates the development of Sjögren’s syndrome in non-obese diabetic mice (HUM3P.256)

Abstract

Abstract Programmed death-ligand 1 (PD-L1) is a B7-family member and plays a negative role in T cell -mediated immunity by binding to its receptors such as programmed death-1 (PD-1). Previous reports have shown enhanced expression of PD-L1 and PD-1 in the salivary gland of patients with Sjögren’s syndrome (SS), a prevalent systemic autoimmune disease characterized by progressive lymphocyte infiltration of exocrine glands and generation of autoantibodies, which together lead to impaired secretory function of salivary and lacrimal glands. However, the particular function of PD-L1 in SS disease development still remains poorly understood. Here we employed non-obese diabetic (NOD) mice, a model of SS-like disease to define the role of endogenous PD-L1 in the pathogenesis of SS. Administration of an anti-PD-L1 antibody to NOD mice enhanced leukocyte infiltration in salivary glands and elevated the levels of serum antinuclear antibodies. Importantly, PD-L1 blockade also has a crucial effect on the clinical phenotype of SS. We demonstrated blockade of PD-L1 markedly reduced salivary secretion, indicating an exacerbated secretory dysfunction. These results suggest that blockade of endogenous PD-L1 promotes the SS-characteristic pathological and clinical changes and accelerates SS development in NOD mice. Further understanding of the molecular mechanisms underlying the function of PD-L1 in SS could identify critical molecular targets for development of alternative therapeutic strategies.