Humanized Mouse Models of Sjögren's Disease

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.