Development of an improved preclinical humanized mouse platform representing the diverse clinical phenotypes of Sjögren’s syndrome

BackgroundSjögren’s syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration of exocrine glands, leading to impaired glandular secretion. To elucidate the pathogenic mechanisms underlying SS, suitable preclinical animal models are essential.

In this study, we developed a humanized murine model that captures key immunopathological features of SS patients, and assessed its therapeutic utility.MethodsPBMCs obtained from SS patients were stimulated with anti-CD3 and anti-CD28 antibodies for 15 hours, and 1 × 106 or 2 × 106 of these cells were intraperitoneally injected into NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice. At 5 weeks after cell injection, pathological analysis and immunophenotypic characterization of infiltrating immune cells within the salivary gland tissues were performed.

To evaluate the efficacy of metformin, NSG mice transplanted with PBMCs were orally administered metformin daily for 5 weeks.ResultsMice injected with PBMCs from SS patients exhibited a significant increase in the frequency of human IL-17-producing T cells in the spleen, accompanied by enhanced infiltration of these pro-inflammatory cells into the salivary glands.