Fig. 2

Primary Sjögren’s syndrome: a back and forth interplay from mouse to man. To investigate the heterogeneous and complex pathogenesis of primary Sjögren’s syndrome (pSS), murine models such as nonobese diabetic (NOD) or NOD-derived mice are indispensable. Knowledge-based implementation derived from mouse models is commonly implemented into human studies and potential clinical trials. As the heterogeneity of patients is often underestimated, we propose a back and forth interplay of knowledge between mouse and man, looping the circle from man to mouse and back. Hereby, models will further be improved to better resemble specific aspects of human disease, essential for both therapeutic development and outcome prediction. An important step will be to compare common deregulated pathways in both mouse and man to address therapeutic manipulations, by isolating whole blood/peripheral blood mononuclear cells (PBMCs) or extracting target tissue biopsies from salivary and lacrimal glands. Patient selection and subgrouping according to their interferon (IFN) signatures, into IFN-positive and IFN-negative subgroups, will require separate mouse models per subgroup. As the NOD mouse most probably represents the subset of systemically IFN-negative patients, we here propose the NOD model revisited: TLR7-induced systemic IFN signature in the NOD mouse as the IFN-positive counterpart, by topical application of the TLR-agonist imiquimod. Furthermore, comparing equal compartments in both subgroups of mice and men will give new insights into both the similarities and differences. Mouse models will remain crucial for preclinical exploration studies and will need continued revisiting and refining. TLR, Toll-like receptor