Tlr9 expression protects against Tlr7-dependent exocrine gland and systemic disease manifestations in primary Sjögren’s disease in a sex-biased manner

Primary Sjogren’s disease (pSD) is a systemic autoimmune disease. Currently, the causes of pSD remain unknown, and no curative therapies are available. Prior studies by our group showed Tlr7 activation was an important driver of pSD in females. Since Tlr7 is regulated by Tlr9, we hypothesized that ablation of Tlr9 would exacerbate disease in a Tlr7-dependent manner. To this end, we generated pSD mice that lacked systemic expression of either Tlr9 (NOD.B10 Tlr9-/-) or both Tlr7 and Tlr9 (NOD.B10 Tlr-DKO). The objective of this study was to determine if Tlr9 mediated sex-biased disease and whether this was dependent on the expression of Tlr7. We analyzed sera from 5 female and 5 male mice of each of the following strains: NOD.B10, NOD.B10 Tlr9 KO, NOD.B10 Tlr-DKO. All mice were aged to the clinical disease stage (26 weeks of age).