TLR7 mediates tissue-specific disease manifestations in primary Sjogren’s disease in a sex-biased manner

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B651
Abstract ID: 4688

Presenting Author:
Achamaporn Punnanitinont , PhD Candidate at Univ. at Buffalo, SUNY

Abstract:

Primary Sjogren’s Disease (pSD) is a systemic autoimmune disorder with a strong female sex-bias that is characterized by multi-organ inflammation. The etiology of pSD remains unknown, and effective treatments are lacking. We hypothesized that systemic ablation of Tlr7 ameliorates pSD in a sex-specific manner. We generated a novel pSD strain that lacked Tlr7 systemically. Inflammation was quantified in exocrine tissues, lungs and kidneys from Tlr7-deficient pSD mice at the clinical disease stage. Flow cytometry was performed on secondary lymphoid tissues. ELISAs and autoantigen arrays were used to examine serum antibodies. Sialadenitis was increased in both female and male Tlr7-deficient pSD mice as compared to Tlr7-sufficient controls. Nephritis was diminished in Tlr7-/- pSD females, while ablation of Tlr7 in males led to exacerbated pneumonitis as compared to age and sex-matched Tlr7-sufficient mice. Female Tlr7-/- pSD mice exhibited reduced Age-associated B cells (ABCs), while pSD males that lacked Tlr7 showed expansion of germinal center B cells, ABCs, and CD4+ activated T cells. Finally, Tlr7-/- females showed decreased serum IgG levels as compared to female Tlr7-sufficient controls. Autoantigen array data revealed IgM from Tlr7-deficient pSD males was enriched for antinuclear-specific autoantibodies as compared to sex-matched controls. Overall, these data indicate that Tlr7 activation is primarily pathogenic in females with pSD, but is protective in males.