Humanized Mouse Models of Sjögren's Disease

Abstract Sjögren's disease (SjD), or Sjögren's syndrome, is a chronic autoimmune condition that targets exocrine glands, leading to dryness symptoms. With the treatment plan for SjD having remained unchanged for the past decade, there is a critical need for innovative therapeutic strategies. To bridge the gap between mouse models and human patients, we have established a mouse model of experimental Sjögren's syndrome with a human immune system (HIS‐ESS). Immunizing mice with antigens derived from human salivary epithelial cells results in HIS‐ESS mice that display clinical features of SjD that include salivary dysfunction, increased serum autoantibodies, and dysregulated immune responses. Effector T cell subsets such as Th1, Th17, and T follicular helper (Tfh) cells are also elevated in HIS‐ESS mice. Thus, this humanized model can effectively recapitulate SjD outcomes and immunopathogenesis, offering a promising platform for drug screening and preclinical research. © 2025 Wiley Periodicals LLC. Basic Protocol : Establishment of humanized mouse models of primary Sjögren's syndrome Support Protocol 1 : Irradiation of neonatal mice Support Protocol 2 : Preparation of proteins from A‐253 human salivary epithelial cells Support Protocol 3 : Determination of mouse saliva flow rate