Fig. 1

Possible role of estrogen in promoting Sjögren’s syndrome. In the context of genetic, epigenetic, and environmental influences like infections and chemicals, the rapid decline in estrogen (E2) levels prior to menopause leads to reduced glandular cell health. Death of glandular cells via apoptosis/necrosis provides self-antigens like nuclear antigens for presentation to the immune system to promote autoimmune disease. At the same time, the protective effects of higher estrogen levels on inflammation disappear allowing increased activation of innate immune pathways like toll-like receptor 4 (TLR4) and NFκB. In contrast, low levels of estrogen continue to increase the level and different types of autoantibodies with age