Recent Advances in Mouse Models of Sjögren's Syndrome

Abstract

Sjögren's syndrome (SS) is a complex rheumatoid disease that mainly affects exocrine glands, resulting in xerostomia (dry mouth) and xerophthalmia (dry eye). SS is characterized by autoantibodies, infiltration into exocrine glands, and ectopic expression of MHC II molecules on glandular epithelial cells. In contrast to the well-characterized clinical and immunological features, the etiology and pathogenesis of SS remain largely unknown. Animal models are powerful research tools for elucidating the pathogenesis of human diseases. To date, many mouse models of SS, including induced models, in which disease is induced in mice, and genetic models, in which mice spontaneously develop SS-like disease, have been established. These mouse models have provided new insight into the pathogenesis of SS. In this review, we aim to provide a comprehensive overview of recent advances in the field of experimental SS.

Keywords: Sjögren's syndrome; autoimmune disease; exocrine glands; mouse model; pathogenesis.

Figure 1

Dysregulated homeostasis in both immune cells and exocrine glands is involved in the development of SS-like disease in mice. On the one hand, abnormal proliferation (HLV1-tax-Tg model), apoptosis of exocrine gland epithelial cells (STAT3 KO, IκB-ζ KO, NOD-derived mice, NFS/sld, TSP-1 KO, Ar KO, and RbAp48-tg mouse models), and ectopic expression of MHC II in the exocrine gland (IQI/Jic, Ro60-peptide immunization, RbAp48-tg, and M3R-immunized models) are suggested to be involved in disease pathogenesis by the corresponding mouse models. On the other hand, APCs (TSP1 KO), CD4 T cells (Aly/Aly, RbAp48-tg, Ar KO, Act1 KO, PI3K KO, and M3R immunization mouse models), B cells (Ar KO, Act1 KO, NOD, Ro60-peptide immunization, BAFF-tg), Treg cells (Ar KO, NFS/sld, IQI/Jic), and cytokines (SG protein immunization) have been suggested to play a role in the development of disease in corresponding mouse models.